54 research outputs found
Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide
The Gram-positive bacterium Streptococcus pneumoniae causes severe disease
globally. Vaccines that prevent S. pneumoniae infections induce antibodies
against epitopes within the bacterial capsular polysaccharide (CPS). A better
immunological understanding of the epitopes that protect from bacterial
infection requires defined oligosaccharides obtained by total synthesis. The
key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide
repeating unit that is not contained in currently used glycoconjugate vaccines
is the assembly of the trisaccharide
β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points
are equipped with orthogonal protecting groups. A linear approach relying on
the sequential assembly of monosaccharide building blocks proved superior to a
convergent [3 + 3] strategy that was not successful due to steric constraints.
The synthetic hexasaccharide is the starting point for further immunological
investigations
Sequential Linkage of Carbohydrate Antigens to Mimic Capsular Polysaccharides: Toward Semisynthetic Glycoconjugate Vaccine Candidates against Streptococcus pneumoniae Serotype 14
Vaccines based on isolated polysaccharides successfully protect humans from bacterial pathogens such as Streptococcus pneumoniae. Because polysaccharide production and isolation can be technically challenging, glycoconjugates containing synthetic antigens are an attractive alternative. Typically, the shortest possible oligosaccharide antigen is preferable as syntheses of longer structures are more difficult and time-consuming. Combining several protective epitopes or polysaccharide repeating units as blocks by bonds other than glycosidic linkages would greatly reduce the synthetic effort if the immunological response to the polysaccharide could be retained. To explore this concept, we bridged the well-understood and immunologically potent RU of S. pneumoniae serotype 14 (ST14) with an aliphatic spacer and conjugated it to the carrier protein CRM197. Mice immunized with the spacer-bridged glycan conjugates produced high levels of specific antibodies after just one or two vaccine doses, while the tetrasaccharide repeating unit alone required three doses. The antibodies recognized specifically ST14 CPS, while no significant antibody levels were raised against the spacer or unrelated CPS. Synthetic vaccines generated antibodies with opsonic activity. Mimicking polysaccharides by coupling repeating unit antigens via an aliphatic spacer may prove useful also for the development of other glycoconjugate vaccine candidates, thereby reducing the synthetic complexity while enhancing a faster immune response
Recommended from our members
Living with multiple disabilities: Design for adult day program facilities
This thesis applies a design programming process to users with multiple, severe disabilities. The goal is to increase independent functioning, self-efficacy and competency through design. The example used in this thesis is the design of day program facilities for adults with multiple, severe disabilities. The existing state of disability in the United States is analyzed. This includes the models of disabilities, historical aspects of the disability movement, the design professions' response, multiple disabilities and day program facilities. Hershberger's Value-Centered programming process is discussed. Its' determinants of architecture are applied to day program facilities and the consumers who attend such programs. Generalized values and issues are presented as background information and applied to a hypothetical design project for a day program facility. Future applications and research are recommended to facilitate the process of including users with special needs in the design programming process
Alien Registration- Claney, James (Orono, Penobscot County)
https://digitalmaine.com/alien_docs/5688/thumbnail.jp
Understanding Residents’ Decision-Making in Urban Regeneration: A Case Study of Kale Neighborhood in Çorum, Turkey
This study examines the decision-making processes of residents in Turkey’s urban regeneration projects employing a single case study, namely, Çorum’s Kale neighbourhood. Çorum is a city with 250,000 inhabitants located in Black Sea Region. The aim is to uncover the factors influencing residents’ acceptance or rejection of urban regeneration and the role of the Turkish government in shaping their decisions. The thesis utilizes a Gramscian theoretical framework and mainly focuses on the fluid relationship between consent and coercion (Fusaro et al., 2017). Methods used in this research include reviewing relevant project documents and newspapers, various types of interviews including semi-structured, go-along and expert interviews, field observations, and photographic documentation of the neighbourhood, along with Tillmann-Healy’s (2003) “Friendship as method” approach capitalizing on the trust between neighbours and the researcher’s grandmother who resides in the investigated urban regeneration site. The literature reveals that the main factors shaping residents’ decisions both globally and in Turkey are the extent of resident participation in these initiatives, the presence of neoliberal authoritarian governance, residents’ socioeconomic positioning, cultural identity, tenure status, informal land ownership and perception of benefits like expanded infrastructure along with enhanced living standards, as well as their fears of forced eviction and displacement. On top of these factors, in Turkey, residents’ decisions are also shaped by fear of expropriation, religious and ethnic disparities, varying laws with different powers and the combination of neoliberal authoritarian governance with Islam. The empirical findings of this thesis suggest that the central issues causing Kale neighbourhood’s residents to reject urban regeneration are the absence of economic advantages provided by the government, which involves undervaluing their existing properties, reselling newly constructed relatively smaller units with higher prices and indebting them with substantial mortgages for extended periods. All in all, this thesis finds that residents’ decision-making process is multifaceted, involving a complex interplay of diverse factors that often affect them concurrently, underscoring the necessity for a holistic examination of their motivations. The thesis contributes to the existing literature by presenting a nuanced analysis of decision-making regarding urban regeneration in a highly polarized and contentious context. Furthermore, it adds to existing studies by presenting research on understudied, peripheral geography in Turkey, offering valuable insights into urban regeneration processes outside of the urban centers
Alien Registration- Claney, James (Orono, Penobscot County)
https://digitalmaine.com/alien_docs/5688/thumbnail.jp
Understanding Residents’ Decision-Making in Urban Regeneration: A Case Study of Kale Neighborhood in Çorum, Turkey
This study examines the decision-making processes of residents in Turkey’s urban regeneration projects employing a single case study, namely, Çorum’s Kale neighbourhood. Çorum is a city with 250,000 inhabitants located in Black Sea Region. The aim is to uncover the factors influencing residents’ acceptance or rejection of urban regeneration and the role of the Turkish government in shaping their decisions. The thesis utilizes a Gramscian theoretical framework and mainly focuses on the fluid relationship between consent and coercion (Fusaro et al., 2017). Methods used in this research include reviewing relevant project documents and newspapers, various types of interviews including semi-structured, go-along and expert interviews, field observations, and photographic documentation of the neighbourhood, along with Tillmann-Healy’s (2003) “Friendship as method” approach capitalizing on the trust between neighbours and the researcher’s grandmother who resides in the investigated urban regeneration site. The literature reveals that the main factors shaping residents’ decisions both globally and in Turkey are the extent of resident participation in these initiatives, the presence of neoliberal authoritarian governance, residents’ socioeconomic positioning, cultural identity, tenure status, informal land ownership and perception of benefits like expanded infrastructure along with enhanced living standards, as well as their fears of forced eviction and displacement. On top of these factors, in Turkey, residents’ decisions are also shaped by fear of expropriation, religious and ethnic disparities, varying laws with different powers and the combination of neoliberal authoritarian governance with Islam. The empirical findings of this thesis suggest that the central issues causing Kale neighbourhood’s residents to reject urban regeneration are the absence of economic advantages provided by the government, which involves undervaluing their existing properties, reselling newly constructed relatively smaller units with higher prices and indebting them with substantial mortgages for extended periods. All in all, this thesis finds that residents’ decision-making process is multifaceted, involving a complex interplay of diverse factors that often affect them concurrently, underscoring the necessity for a holistic examination of their motivations. The thesis contributes to the existing literature by presenting a nuanced analysis of decision-making regarding urban regeneration in a highly polarized and contentious context. Furthermore, it adds to existing studies by presenting research on understudied, peripheral geography in Turkey, offering valuable insights into urban regeneration processes outside of the urban centers
Rockingham ware in America, 1830–1930: An exploration in historical archaeology and material culture studies
Historical archaeologists depend upon artifacts as the prime source of information about past occupants of sites from which the artifacts were excavated. These artifacts are analytically useful only to the degree that their meanings and uses in historical context are understood. Documents or other imagery from the time the artifacts were used and deposited are principal providers of this essential information. But some of the most ubiquitous artifacts found in the archaeological record—small, ordinary household things, which should by the fact of their daily presence in the lives of their owners tell us about those lives—were too commonplace and unremarkable to have been discussed much in the historical record. In a turnabout of procedure, information from the archeological sites themselves may become the primary data sets for understanding these heretofore little understood artifacts and their meaning systems. For historical archaeologists have linked a vast number of artifacts with their historical owners and their owners\u27 cultural universe, and these data are available. They can be synthesized to see if discernible patterns of use existed. Rockingham ware was an inexpensive nineteenth-century ceramic widely used in America but hardly mentioned in period documents. I conducted a material culture study of Rockingham ware from two approaches. The first situates Rockingham ware in the context of its production history, which was unique in the history of anglo-American ceramics. The second uses information from artifact assemblages and archaeological site reports to identify patterns of distribution. These demonstrate that while the analysis of Rockingham ware usage per se produced a flat curve, the factors of gender, class, and rural or urban location—and intersections of these factors—markedly affected the choice of vessel forms in Rockingham ware. Plausible explanations of these patterns were forthcoming from documentary sources treating the cultural milieus of Rockingham-ware users. Hints and clues from a variety of sources converged to reveal ways in which certain Rockingham-ware vessels, even so lowly a household item as a Rockingham-ware mixing bowl, were used to negotiate social change and to express and reinforce cultural meanings
Rockingham ware in America, 1830–1930: An exploration in historical archaeology and material culture studies
Historical archaeologists depend upon artifacts as the prime source of information about past occupants of sites from which the artifacts were excavated. These artifacts are analytically useful only to the degree that their meanings and uses in historical context are understood. Documents or other imagery from the time the artifacts were used and deposited are principal providers of this essential information. But some of the most ubiquitous artifacts found in the archaeological record—small, ordinary household things, which should by the fact of their daily presence in the lives of their owners tell us about those lives—were too commonplace and unremarkable to have been discussed much in the historical record. In a turnabout of procedure, information from the archeological sites themselves may become the primary data sets for understanding these heretofore little understood artifacts and their meaning systems. For historical archaeologists have linked a vast number of artifacts with their historical owners and their owners\u27 cultural universe, and these data are available. They can be synthesized to see if discernible patterns of use existed. Rockingham ware was an inexpensive nineteenth-century ceramic widely used in America but hardly mentioned in period documents. I conducted a material culture study of Rockingham ware from two approaches. The first situates Rockingham ware in the context of its production history, which was unique in the history of anglo-American ceramics. The second uses information from artifact assemblages and archaeological site reports to identify patterns of distribution. These demonstrate that while the analysis of Rockingham ware usage per se produced a flat curve, the factors of gender, class, and rural or urban location—and intersections of these factors—markedly affected the choice of vessel forms in Rockingham ware. Plausible explanations of these patterns were forthcoming from documentary sources treating the cultural milieus of Rockingham-ware users. Hints and clues from a variety of sources converged to reveal ways in which certain Rockingham-ware vessels, even so lowly a household item as a Rockingham-ware mixing bowl, were used to negotiate social change and to express and reinforce cultural meanings
- …