1,721,373 research outputs found
Synthesis of neisseria meningitidis x capsular polysaccharide fragments
No full textN. meningitidis type X (Men X), first described in the 1960s1, has been found to cause a few cases of invasive disease and in 2006 WHO started to consider Men X as a substantial threat, when an unprecedented incidence of meningitis caused by Men X was observed in Niger and in Western Kenya. The development of carbohydrate-based vaccines has recently emerged as a possible approach with enormous potential benefits for human health. Since capsular polysaccharides (CPSs) are the key virulence factors for encapsulated bacteria, the development of more comprehensive conjugate vaccines including Men X CPS fragments become an urgent issue in the near future.
The CPS of N. meningiditis X is a linear homopolymer of (14)-linked 2-acetamido-2-deoxy-alpha-D-glucopyranosyl phosphate residues, with an average chain length of 50 units.
The present research project is focused on the synthesis of phosphodiester-linked oligomers of the native Men X CPS. In order to improve the immune response of the synthesized oligomers they will be employed in the synthesis of neo-glycoconjugates by exploiting the amino group of the spacer arm at the reducing end of each fragment
Synthesis of Neisseria meningitidis X capsular polysaccharide fragments
No full textSerotype X of Neisseria meningitidis bacterium (Men X) recently emerged as a substantial threat to public health. Since anti-meningococcal vaccines currently available or under investigation do not contain antigenic components of Men X capsular polysaccharide, there is the need to develop more comprehensive conjugate vaccines capable to offer higher protection. As a preliminary step towards this goal, the synthesis of three conjugatable Men X capsular polysaccharide fragments is described. The installation of the crucial α-glycosyl phosphodiester linkages is based on the hydrogenphosphonate methodology using pure α-glycosyl hydrogenphosphonates 10 and 12 obtained from hemiacetals 9 and 11, respectively
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
SYNTHESIS AND CONJUGATION OF NEISSERIA MENINGITIDIS X CAPSULAR POLYSACCHARIDE FRAGMENTS
Full text linkBacterial meningitis has still a profound impact on public health. Worldwide, approximately 1,200,000 cases (with more than 170,000 deaths) of bacterial meningitis are recorded annually, and over 80% of them are caused by three encapsulated bacteria, Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b. These pathogens are responsible of 40% of the total mortality cases by infectious diseases in infants and young children. More than twelve different serogroups of N. meningitidis have so far been defined, but about 90% of the infections are due to serogroups A, B, C, Y and W135. However, in the past 20 years sporadic cases or clusters of meningitis due to other N. meningitidis serogroups, such as N. meningitidis type X (Men X), have emerged. In 2006, WHO declared Men X as a substantial threat, highlighting the urgency for developing a vaccination protocol including this serotype. Indeed, vaccines currently available on the market against meningococcal disease, as well as those under licence, do not include antigenic components of Men X, and therefore they do not offer protection against infections caused by this emerging serogroup.
It is well established that capsular polysaccharides (CPSs) are the key virulence factors for encapsulated bacteria. Therefore, the development of anti-MenX vaccines based on MenX CPS as antigenic components has emerged as a possible approach with enormous potential benefits for human health. However, as polysaccharides are T-independent antigens, purified CPS-based vaccines are poorly immunogenic in infants and young children, and they fail to establish immunological memory. As a consequence, an efficient saccharide-based vaccine against MenX should be composed of glycoconjugates, where the CPSs (or their synthetic fragments) are conjugated to carrier proteins, thus eliciting a T-dependent response which enhances the immunogenic properties of the saccharide moiety and leads to the re-establishment of the immunological memory.
The CPS of N. meningiditis X is a homopolymer of (1→4)-linked 2-acetamido-2-deoxy--D-glucopyranosyl phosphate residues. The present PhD thesis describes the synthesis of phosphodiester-linked oligomers (monomer, dimer and trimer) of the native Men X CPS, and the corresponding neo-glycoconjugates with appropriate immunogenic protein carriers. Each oligomer is endowed of a phosphodiester-linked aminopropyl spacer at its reducing end to allow protein conjugation.
The first part of the synthetic endeavour has been devoted to the preparation of a suitably protected monosaccharide precursor of the synthetic route. Next, the synthetic strategy has been implemented by unblocking of the anomeric position and coupling via a phosphodiester bridge with the N-protected aminopropyl spacer. Then, the delivery of 4-OH, followed by a second coupling via a phosphodiester bridge provided the corresponding dimer. The iteration of the above protocol led to the target oligomers. In all cases, the phosphodiester linkages were installed via the well-established H-phosphonate approach. Noteworthy, two different synthetic routes towards Men X oligomers have been explored, and they are critically analysed and discussed in the text.
Finally, in order to improve the immune response of the synthesized oligomers, they were covalently linked to carrier proteins by exploiting the amino group of the spacer arm at the reducing end and employed in the synthesis of neo-glycoconjugates
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
Synthesis of Fragment of beta-Glucans as Potential Ligands for Dectin-1
No full textBeta-glucans are glucose polymers linked together by a 1,3 linear beta-glycosidic chain core, differing from each other by their length and branching configuration. The branches derived from the glycosidic chain core are either 1,4 or 1,6 glycosidic chains and appear to be dependent on the source.
Dectin-1 is a unique C-type lectin that recognizes beta-glucan carbohydrates present on the surface of various fungi, including C. albicans. Its activation promotes microbial uptake and phagocytosis, but also mediates, in synergy with TLRs, the production of cytokines such as IL-12 and TNF alfa, leading ultimately to the initiation of the adaptive immune response. For this reason, beta-glucans – or their fragments – can be referred to as a possible class of adjuvants to increase the immune response to pathogens. In addition, the administration of beta-glucan-derived compounds can help in gaining new insights on the mechanism of action of dectin-1 receptor.
Dectin-1 binds beta-glucan polymers with affinities ranging from very low (3x10-3 M) to very high (2x10-12 M). The wide range of affinities appears to be due to the differing sizes and numbers of branches in -glucans from various sources.
Although the interaction between Dectin-1 and beta-glucans has been supposed to involve a conformational epitope as a high order local helix, little is known about the binding mode and the degree of (1-6)-branching of the glucan chain in the binding epitope. For this reason, a series of fragments of beta-glucans, differing in the 6-O branching degree, has been synthesised. Their ability to bind to dectin-1 and of activating the inflammatory response will be subsequently tested
- …
