1,721,283 research outputs found

    Defeating antibiotic-resistant bacteria with protein-resistant polyGGE film

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    Biofouling on medical device surfaces, which is initiated by protein adsorption and adhesion of microbes especially the antibiotic-resistant bacteria, attracts global attention for centuries due to its enduring challenges in healthcare. Here, the antifouling effect of hydrophilic poly(glycerol glycidyl ether) (polyGGE) film is explored in comparison to hemocompatible and protein-resistant control polymers. The chemical and thermomechanical stability of polyGGE in hydrated conditions at body temperature was achieved via adjusting UV curing and KOH quenching time. The polyGGE surface is inert to the plasma protein adsorption and interfered the metabolism conditions, biofilm formation and growth of both Gram negative (Gram-) and antibiotic-resistant Gram positive (Gram+) bacteria. These results indicate the potential application of polyGGE for combating the risk of hospital-acquired infections and preventing drug-resistant superbug spreading

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Stem Cell Instruction via Appropriate Geometry and Local Curvature of Microstructured Polymeric Substrates

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    Stem cells hold a great potential for regenerative therapy due to their properties of self-renewal, differentiation potential, homing ability, pro-angiogenic secretion and immunoregulation. With the help of biomaterials, stem cells can potentially be adapted since the physicochemical properties of biomaterials are able to guide the regenerative therapy towards the desired goals and augment the therapeutic efficacy by modulating cell fate and the regeneration process. Therefore, the understanding of stem cell-material interaction and the underlying mechanism is essential for designing biomaterials that are qualified for regenerative applications. Different cell types or same type of stem cells derived from different species may differ in response to the physicochemical factors from the different materials and to the same material with different microstructures according to their size, phenotype and sensing approach. Here, rat bone marrow-derived MSCs, human adipose derived-MSCs and mouse iPSCs were used. The study of bone marrow derived-MSCs (Chapter 3.1) was focused on the intrinsic physicochemical properties of PEI and PEU with similar wettability. They both were applied as polymeric inserts to ensure that the MSCs were exclusively in contact with the target polymers, and served as culture vessels for long-term maintenance of MSCs in vitro. Previously, we have investigated the cell compatibility of different polymers including PEI and PEU with human bone marrow-derived MSCs. The cell shape was altered and the alignment of F-actin cytoskeleton was reorganized in a random way in PEU. Among the tested polymers, PEI could support the long-term maintenance of human MSC self-renewal state. Similarly, for rat MSCs, flat and enlarged shape with rearranged F-actin cytoskeleton was observed for cells growing on PEU, while cells on PEI and TCP shared a typical spindle-shaped morphology and F-actin orientation. Although cells could grow on both polymeric surfaces with the similar adhesion ratio and subsequent division rate, cells cultured on PEU exhibited lower cell density after 5 days culture, which may directly attribute to the higher apoptosis level and senescence ratio. In this context, PEI provided relatively better cell compatibility for rat MSC survival and growth. Regardless of implementing a human or rat system, among all the tested polymers, PEI proved to be or was observed to be the most appropriate polymer substrate for bone marrow-derived MSCs culture. Strikingly, compared to the cells growing in traditional culture conditions with TCP and the human MSCs growing in PEU and PEI, both substrates could trigger rat MSCs towards spontaneous adipogenesis. Besides the effects that different chemical compositions of polymeric surfaces have on cells, the stem cell-mediated reflection to the polymer surface or the entire microenvironment at the cell-material interface may also differ due to species or other issues. These issues may play a certain role in differentiation, however, they still need to be further clarified. In this thesis, for the study of human adipose-derived MSC response to micro-scale geometric cues (Chapter 3.2 and 3.3), microstructured substrates comprising arrays of square-shaped or round-shaped microwells were developed as a transitional model between 2D and 3D systems. Initially after seeding, cells were likely to roll into the microwells instead of adopting a random distribution. Post spreading, MSCs moved freely on both microstructured substrates without physical constraints. In spite of the free cell migration, different migration velocities were observed on different microstructured substrates. The cell morphologies were three-dimensionally modulated by the local curvature of microwell structure due to differences in focal adhesion and alterations of the cytoskeleton. In contrast to the substrate with round-shaped microwells, the substrate with square-shaped microwells promoted the secretion of angiogenic factor IL-6, proliferation and osteogenesis of MSCs. Such microwell shape-dependent modulatory effect was highly associated with ROCK signaling. Following ROCK inhibition, the differences in IL-6 secretion, proliferation and osteogenesis between cells on different substrates were diminished. These findings allow a better understanding of MSC response to geometric cues and highlight the possibility to control the fate and functions of MSCs through structured features via manipulation of ROCK signaling. This knowledge might help to direct stem cells towards desired orientations and functions through utilization of biomaterial surface structures. As indicated in Chapter 3.2 and 3.3, the distinct local curvature of square and round-shaped microwells was considered as a potential trigger and regulatory factor involved in modulation of MSC cellular response. In Chapter 3.4 and 3.5, a series of microroughness surfaces with local micro-scale curvature change were created. Surfaces with an appropriate microcurvature relevant to a single MSC size (PS-160) could effectively enhance the VEGF secretion and the pro-angiogenic effect of human adipose-derived MSCs via integrin-activation initiated intracellular signaling cascades (e.g FAK and ERK). The functional cardiomyogenic differentiation together with pro-angiogenic secretion of mouse iPSCs was boosted and mechanically memorized initially via cell compacting and later on via strengthening of cell-cell junctions by local curvatures fitting to EB diamension (PEI R2). We speculated that both mechanosensors E-cadherin and YAP might be the potential determinants. Further studies need to be carried out. Regardless of various MSC sources (adipose tissue- and bone marrow-derived) and different types of stem cells (MSCs and iPSCs), both 2.5D microstructuring with different local curvatures and polymeric substrates with different chemical components can modulate stem cell morphology and behavior, and provide the basis for development and future commercialization in tissue culture systems. This approach of induced and controlled endogenous regeneration using a polymeric biomaterial may also be applicable to other stem/progenitor cells and to various types of implants, such as microstructured substrates of orthopedic implants, where the integration into relevant tissues could potentially be improved. Further, with the introduction of microtechnological platforms for cell culture, the pace of stem cell research can be dramatically enhanced

    Modulation des mesenchymalen Stammzellen Verhaltens durch Temperatur- und mechanische Belastung Stimulation

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    Different physical cues are known to affect mesenchymal stem cell (MSC) behavior, indicating a complex relationship between the cell and its microenvironment. Mechanical strain and temperature changes are examples of cues that are relevant in vitro and in vivo. However, the combined effects of multiple physical cues on MSCs remained unclear. Traditional mechanical devices used in cell research have limitations on the integration of various factors and high-throughput applications. The requirement of new biomaterials to integrate the multiple external stimuli was arising to figure out the complex cellular mechanisms. The thermoresponsive mechanical strain was investigated to achieve the aim of using active biomaterials to study the combined effects on human MSCs. Poly (ℇ-caprolactone)-butyl acrylate (PCL-BA) copolymer sheet actuators were programmed so that the reversible shape change could be controlled by temperature changes between 37 °C and 10 °C. A thermochamber was used to culture the human adipose-derived stem cells (ADSCs) on the shape-memory polymer sheet actuators. 50 × 50 µm grids were created on the underside of the actuator sheets to observe the shape change of polymer and cells. Cell morphology, orientation, and migration were observed and recorded using time-lapse microscopy. The dual stimuli of temperature change and mechanical strain were translated into intracellular signals, such as calcium oscillation and nuclei translocation of the mechanical sensors, which were characterized using chemical reagents and immunostaining. Further, epigenetic histone modification of hADSCs was analyzed using chromatin immunoprecipitation quantitative real-time PCR (ChIP-qPCR). Finally, adipogenesis and osteogenesis of the hADSCs were studied to evaluate MSC differentiation capacity with the combined physical cues. The effect of temperature changes on adipocyte dedifferentiation was demonstrated by quantifying lipid accumulation in mature adipocytes. The expression of lipid accumulation-related genes and cell proliferation capacity were analyzed to investigate the dedifferentiation properties. In this work, the PCL-BA shape-memory polymer actuator elongated more than 10% at 10 °C, and contracted when returned to 37 °C. The mechanical strain was generated with the polymer actuator's elongation, which modified the cell morphology and increased cell migration. The periodic temperature change and mechanical strain induced calcium influx into cells; meanwhile, the mechanical strain promoted nuclei translocation of the YAP and RUNX2. The dual stimuli further increased the epigenetic acetylation of histone H3 lysine 9 (H3K9ac) and enhanced the expression level of osteogenesis-related genes and proteins. In addition, the dual stimuli of temperature change and mechanical strain induced the focal adhesion activation by regulation of integrin and myosin light chain (MLC) phosphorylation. As a result, cytoskeleton organization and focal adhesion activation were reduced by pretreatment of the MSCs with temperature changes but enhanced with mechanical strain changes. Temperature change alone decreased the cell migration velocity on SMPA substrate, while temperature change and mechanical strain combined increased cell migration velocity. Further, the cyclic temperature change (10 - 37 °C) decreased intracellular lipid of mature adipocytes and increased free fatty acids (FFA) outside. Simultaneously, mature adipocyte marker FABP4 was significantly down-regulated, while the brown adipocyte-related genes UCP1, PGC-1α, and PRDM16 were up-regulated. Ki67 represents the proliferation marker that was increased after the treatment of temperature change. The transformation of mature adipocytes and increasing proliferation capacity indicates the promotion of adipocyte dedifferentiation. The shape-memory polymer actuator sheet is an active biomaterial that can generate mechanical strain with simple temperature control. This artificial muscle allows the combined influence of multiple physical cues on stem cells to be studied. We found the combinative effects of the interplay of mechanical and temperature stimuli on MSC behavior and lineage commitment change, instead of the typical single effect on MSCs. We also established the adipocyte dedifferentiation with periodic temperature changes, which might be used to generate alternative stem cell sources and improve the MSC-based cell therapy in regenerative medicine.Verschiedene physikalische Hinweise das Verhalten mesenchymaler Stammzellen (MSC) beeinflussen, was auf eine komplexe Beziehung zwischen der Zelle und ihrer Mikroumgebung hindeutet. Mechanische Belastung und Temperaturänderungen sind Beispiele für Hinweise, die in vitro und in vivo relevant sind. Die kombinierten Auswirkungen mehrerer physischer Hinweise auf MSCs blieben jedoch unklar. Herkömmliche mechanische Geräte, die in der Zellforschung verwendet werden, haben Einschränkungen bei der Integration verschiedener Faktoren und Anwendungen mit hohem Durchsatz. Um die komplexen zellulären Mechanismen zu verstehen, entstand der Bedarf an neuen Biomaterialien, um die vielfältigen externen Reize zu integrieren. Die thermoresponsive mechanische Belastung wurde untersucht, um das Ziel zu erreichen, aktive Biomaterialien zu verwenden, um die kombinierten Wirkungen auf menschliche MSCs zu untersuchen. Aktuatoren aus Poly(ℇ-caprolacton)-butylacrylat (PCL-BA)-Copolymer wurden so programmiert, dass die reversible Formänderung durch Temperaturänderungen zwischen 37 °C und 10 °C gesteuert werden konnte. Eine Thermokammer wurde verwendet, um die humanen Fettstammzellen (ADSCs) auf den Formgedächtnis-Polymerplattenaktoren zu kultivieren. Auf der Unterseite der Aktorplatten wurden 50 × 50 µm Raster erzeugt, um die Formänderung von Polymer und Zellen zu beobachten. Zellmorphologie, Orientierung und Migration wurden beobachtet und unter Verwendung von Zeitraffermikroskopie aufgezeichnet. Die dualen Stimuli von Temperaturänderung und mechanischer Belastung wurden in intrazelluläre Signale wie Calciumoszillation und Kerntranslokation der mechanischen Sensoren übersetzt, die mit chemischen Reagenzien und Immunfärbung charakterisiert wurden. Darüber hinaus wurde die epigenetische Histonmodifikation von hADSCs mittels quantitativer Chromatin-Immunpräzipitations-PCR (ChIP-qPCR) analysiert. Schließlich wurden Adipogenese und Osteogenese der hADSCs untersucht, um die Differenzierungskapazität von MSCs mit den kombinierten physikalischen Hinweisen zu bewerten. Die Wirkung von Temperaturänderungen auf die Dedifferenzierung von Adipozyten wurde durch die Quantifizierung der Lipidakkumulation in reifen Adipozyten gezeigt. Die Expression von Lipidakkumulations-bezogenen Genen und die Zellproliferationskapazität wurden analysiert, um die Dedifferenzierungseigenschaften zu untersuchen. In dieser Arbeit dehnte sich der PCL-BA-Formgedächtnis-Polymeraktor bei 10 °C um mehr als 10 % aus und zog sich bei Rückkehr auf 37 °C zusammen. Die mechanische Spannung wurde durch die Dehnung des Polymeraktors erzeugt, was die Zellmorphologie veränderte und die Zellmigration verstärkte. Die periodische Temperaturänderung und die mechanische Belastung induzierten einen Calciumeinstrom in die Zellen; währenddessen förderte die mechanische Belastung die Kerntranslokation von YAP und RUNX2. Die dualen Stimuli erhöhten die epigenetische Acetylierung von Histon H3 Lysin 9 (H3K9ac) weiter und erhöhten das Expressionsniveau von Osteogenese-bezogenen Genen und Proteinen. Darüber hinaus induzierten die dualen Stimuli von Temperaturänderung und mechanischer Belastung die fokale Adhäsionsaktivierung durch Regulation der Integrin- und Myosin-Leichtketten-(MLC)-Phosphorylierung. Als Ergebnis wurden die Zytoskelett-Organisation und die fokale Adhäsionsaktivierung durch die Vorbehandlung der MSCs mit Temperaturänderungen reduziert, aber durch mechanische Belastungsänderungen verstärkt. Die Temperaturänderung allein verringerte die Zellmigrationsgeschwindigkeit auf dem SMPA-Substrat, während Temperaturänderung und mechanische Belastung kombiniert die Zellmigrationsgeschwindigkeit erhöhten. Darüber hinaus verringerte die zyklische Temperaturänderung (10 - 37 °C) das intrazelluläre Lipid reifer Adipozyten und erhöhte die freien Fettsäuren (FFA) außerhalb. Gleichzeitig wurde der reife Adipozytenmarker FABP4 signifikant herunterreguliert, während die braunen Adipozyten-verwandten Gene UCP1, PGC-1α und PRDM16 hochreguliert wurden. Ki67 stellt den Proliferationsmarker dar, der nach der Behandlung der Temperaturänderung erhöht war. Die Transformation reifer Adipozyten und eine zunehmende Proliferationskapazität weisen auf die Förderung der Adipozyten-Dedifferenzierung hin. Die Aktorfolie aus Polymer mit Formgedächtnis ist ein aktives Biomaterial, das mit einfacher Temperaturkontrolle mechanische Spannungen erzeugen kann. Dieser künstliche Muskel ermöglicht es, den kombinierten Einfluss mehrerer physikalischer Signale auf Stammzellen zu untersuchen. Wir fanden die kombinatorischen Effekte des Zusammenspiels von mechanischen und Temperatur-Stimuli auf das MSC-Verhalten und die Veränderung der Abstammungslinie anstelle des typischen Einzeleffekts auf MSCs. Wir haben auch die Adipozyten-Dedifferenzierung mit periodischen Temperaturänderungen etabliert, die verwendet werden könnte, um alternative Stammzellquellen zu generieren und die MSC-basierte Zelltherapie in der regenerativen Medizin zu verbessern

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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