1,721,154 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Gene delivery with cationic lipids: fundamentals and potential applications
Full text linkPrinciple of gene therapy.
Although the objectives and principles of gene therapy have been well-defined over the last decades, its application as a versatile, therapeutically successful approach has not yet met expectations. At the onset, the primary goal of gene therapy was to replace a deficient gene in a genetically inherited disease with a normal copy, thereby restoring production of a functional protein. Soon afterwards, this goal was extended to include genetic defects beyond inherited disorders, since modulation of the regulation of gene expression was also involved in numerous acquired diseases. The potential of gene therapy for therapeutic applications thereby grew with the comprehension of mechanisms of diseases and the implication of genes in these events. Nowadays, it is clear that gene therapy not only may lead to its primary goal of replacing a deficient gene, but it could also lead to a modulation of the expression of genes acting on the physiology of malignant cells. Furthermore, by means of gene therapy, functions might be integrated into cells that are not originally present and that could serve a therapeutic purpose. Thus in a modern concept, gene therapy refers to the potential use of nucleic acids, irrespective of whether it concerns plasmid DNA, antisense oligonucleotides or siRNA, to modulate in any kind of way the expression of genes in cells for therapeutic purposes.
Viral and non-viral gene delivery.
Depending on the vectors used for nucleic acid transfer, gene delivery is roughly divided into two main categories: viral and non-viral gene delivery. The first vectors developed were based on using viruses or pseudo-viral particles, exploiting their ability to penetrate the cell for intracellular delivery of their genome in order to use the host machinery for the production of viral proteins. Because of their immunogenicity and potential oncogenicity, possibly resulting from mutational insertion defects when the viral genome integrates into the host genome, viral vectors may pose serious problems in terms of safety, thus jeopardizing their use as therapeutic drugs. Cationic lipids and cationic polymers can be used as well to complex nucleic acids, thereby forming so-called lipoplexes and polyplexes, respectively, and these complexes have been shown to similarly deliver genes into the cells. As opposed to the viral vectors, these systems are collectively known as non-viral gene delivery systems. Moreover because they are immunologically inert these vectors are thought to be safer in vivo. In contrast to viral particles they are not limited to the delivery of coding nucleic acids but can accommodate a greater variety of cargo, including antisense ODNs, siRNAs and entire genes. Finally, non-viral vectors are easier to produce and better amenable to chemical modifications for the purpose of effectuating therapeutic applications. However the major drawback of non-viral vectors is a lower efficiency in transfection, especially in vivo, that hinders their use for in vivo therapeutic applications. Therefore, a better knowledge of the mechanism of transfection mediated by non-viral vectors will allow the development of more efficient non-viral vectors for gene therapy applications.
Scope of the thesis.
This thesis focuses on the biophysical parameters that govern the transfection efficiency of lipoplexes prepared from different classes of cationic lipids, the molecular mechanisms involved in the transfection process and the potential of these novel vectors for in vivo gene therapy. Chapter 2 is reviewing biophysical parameters that influence lipoplex assembly, interaction of lipoplexes with cells, and intracellular delivery of nucleic acids. In the experimental chapters of this thesis we particularly focused on the mechanisms of transfection, mediated by two cationic lipid systems. In chapters 3 and 4 the focus was on the synthetic amphiphile SAINT-2, used in combination with DOPE, to deliver antisense ODNs. In chapter 3 the effect of PEG-lipid analogues on the delivery of antisense ODNs by SAINT-2/DOPE lipoplexes was studied. We demonstrated that the exchangeable properties of the PEG-lipid analogues were instrumental in obtaining effective and functional delivery of antisense ODNs into cells. In chapter 4, in a perspective of non-invasive antisense therapy to the brain, the interaction of lipoplexes with an in vitro model of the blood-brain barrier, in terms of toxicity and eventual transport, was examined. A detailed account is presented on the validity of the polarized cell model used for transcellular transport of lipoplexes. In chapter 5 and 6, the use of a new class of pH-sensitive sugar-based gemini surfactants as cationic lipids for gene delivery was assessed. In chapter 5 a study is described of five different sugar-based gemini surfactants and their transfection efficiency in vitro and in vivo. In chapter 6, the mechanism of transfection, mediated by the two most potent gemini surfactants, was investigated and the effect of the pH on the phase behavior of these lipoplexes in mediating gene delivery by their capacity to disrupt endosomal membranes, is highlighted. Finally, in chapter 7, the work presented in this thesis is summarized and discussed in light of near-future perspectives in the development of cationic lipids for gene delivery purposes.
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
On the cause of multiple sclerosis: Molecular mechanisms regulating myelin biogenesis
Full text linkHoe myeline wordt gemaakt en hoe die kennis van nut kan zijn om een effectieve therapie voor MS te ontwikkelen. Myeline, de vette isolatielaag rondom zenuwcellen, raakt bij multiple sclerose (MS)-patiënten beschadigd door onder andere ontstekingsreacties. Die beschadigingen worden op den duur niet meer hersteld. Om te begrijpen waarom dat niet meer gebeurt, is het belangrijk te weten hoe in normale situaties de myelinemembranen worden gevormd. Met die kennis verwachten we gereedschap in handen te krijgen om de aanmaak van nieuw myeline in de aangetaste gebieden (‘laesies’) weer in gang te zetten en zo de beschermende myeline-laag weer op te bouwen. In dit onderzoek hebben we o.a. inzicht gekregen in de wijze waarop de twee belangrijkste myeline eiwitten, MBP en PLP, beïnvloed kunnen worden in de aanmaak van myeline. Zo hebben we bijvoorbeeld waargenomen dat wanneer de aanmaak van syntaxine 4, een bekend ankereiwit in transportprocessen, in voorlopercellen van oligodendrocyten wordt geblokkeerd, er geen MBP eiwit meer wordt ingebouwd in het myeline. Ook hebben we vastgesteld dat de transportroute van PLP verandert, wanneer in rijpere oligodendrocyten MAL eiwit – een transport-regulerend eiwit – wordt gemaakt. Maar ook factoren van buiten de cel hebben invloed op de aanmaak van myeline. Zoals de ontstekingsmediator TNFα, aanwezig in MS laesies, die ervoor zorgt dat het geraamte van de cel (cytoskelet) in volwassen oligodendrocyten dusdanig wordt aangetast, dat het MBP eiwit niet meer volledig in myeline terechtkomt. Dit onderzoek geeft nieuw en gedetailleerd inzicht in de moleculaire mechanismen die de lokalisatie van de belangrijkste myeline componenten reguleren, en daarmee de myeline aanmaak. Deze resultaten kunnen in de toekomst helpen om nieuwe behandelingen voor MS te ontwikkelen
Multiple sclerosis, remyelination and the role of fibronectin
Full text linkOur central nervous system functions, among others, thanks to myelin. Myelin is a fatty layer of insulation among nervous cells, which is produced by specific cells, namely oligodendrocytes. Multiple sclerosis (MS) is a disease that damages myelin. These myelin injuries (lesions) seem largely responsible for the disease burden of MS. Often, these myelin injuries are permanent in MS, but sometimes myelin recovers spontaneously. This suggests that oligodendrocytes are capable of producing new myelin, but usually do not succeed. What signals prevent oligodendrocytes from producing new myelin in MS lesions? In this thesis, it was investigated how the signal molecule fibronectin influences oligodendrocytes. In these studies, it was discovered that, after myelin injury, fibronectin is ‘automatically’ produced by neighbor cells, including cells named astrocytes. This fibronectin normally promotes recovery of myelin by attracting young progenitor cells of oligodendrocytes. When these progenitors mature to become oligodendrocytes, fibronectin is degraded. However, in MS, fibronectin is not degraded, but accumulates en binds to form aggregates. These fibronectin aggregates were found to impair myelin regeneration by oligodendrocytes. In line with this, fibronectin aggregates are not present in recovered MS lesions. Finally, fibronectin aggregates may stimulate inflammatory reactions of inflammatory cells, named microglia and macrophages. Hence, the observations presented in this thesis suggest that interfering with fibronectin aggregation could contribute to promoting myelin regeneration in MS
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