Nucleic Acid Carriers Based on Precise Polymer Conjugates

Polymer polydispersity, random conjugation of functional groups, and poorly understood structure–activity relationships have constantly hampered progress in the development of nucleic acid carriers. This review focuses on the synthetic concepts for the generation of precise polymers, site-specific conjugation strategies, and multifunctional conjugates for nucleic acid transport. Dendrimers, defined peptide carriers, sequence-defined polyamidoamines assembled by solid-phase supported synthesis, and precise lipopeptides or lipopolymers have been characterized for pDNA and siRNA delivery. Conjugation techniques such as click chemistries and peptide ligation are available for conjugating polymers with functional transport elements such as targeting or shielding domains and for direct covalent modification of therapeutic nucleic acids in a site-specific mode

A Comparison of Quality of Life Measures in Husbands of Women with Breast Cancer

The Quality of Well-Being Scale (QWB-SA) and Medical Outcome Study SF-36 short form (SF-36) are popular health-related quality of life (HRQOL) assessment tools; however, it is unclear whether these measures overlap enough to be interchangeable, and if not, which might be a better choice. This study examined conceptual overlap, validity, and relation with psychosocial functioning of the QWB-SA and SF-36 in a sample of partners of women undergoing adjuvant treatment for breast cancer. Partners (n = 79) of breast cancer patients, recruited in a chemotherapy infusion clinic, completed the QWB-SA and SF-36 and additional psychosocial measures. Descriptive content review shows that both instruments provide a breadth of HRQOL coverage including physical health, mental health, social functioning, role functioning and general health perceptions; however, more QWB-SA scales suffered floor effects. Subscales correlated, with the strongest correlations between the QWB-SA total score and the mental health scales of the SF-36. The QWB-SA and the SF-36 Mental Health Component Summary score, but not the SF-36 Physical Component Summary score were strongly correlated to measures of mood, satisfaction with life, burden, and social support. The QWB-SA and SF-36 measure distinct aspects of HRQOL. Each instrument presents distinct advantages and disadvantages in coverage of particular domains. Labels assigned to SF-36 scales more accurately reflect what they measure. The SF-36 appeared more sensitive to the impact that psychological health played on overall assessment of HRQOL in these partners

James and Shakespeare: Unification Through Mapping

The art of exploration became an important aspect of theater in early modern England. Exploration is typically done through the utilization of a map. The map scene in Lear provides a focal point to peer into the political ventures of King James I. As a proponent for peace, James both unified and divided his kingdom of Great Britain and Ireland through the use of cartography as a way to show the aspirations of a king. Lear, in dividing his kingdom between his three daughters, shows Shakespeare\u27s careful strategic planning of the division of a kingdom and what that means in early modern England.While the map scene in Lear forces us to look more closely at the land that is represented on the map, the scene also forces us to look at how the land is represented on the map. Prior criticism has focused on the division of Lear\u27s lands, but this paper forces us to look at how Lear divides and also how he unifies. This strategy of unification and division mirrors the political strategy of James through his own division and unification tactics. This thesis will focus both on how Shakespeare represents the map in the confines of a play and how the political struggles of a king are represented in that pla

Computational simulation of skull fracture patterns in pediatric subjects using a porcine model

In cases of suspected child abuse with skeletal trauma, it is often the role of the injury biomechanist, forensic pathologist, clinical radiologist, and forensic anthropologist to determine the mechanism of injury when the child victims cannot speak for themselves. This is a challenging task, especially for the head, as comprehensive biomechanical data on skull fracture in infants and children do not currently exist, and frequently the determination regarding cause of injury is based on anecdotal evidence from the medical literature and unsubstantiated eyewitness accounts. The current process may result in unreliable autopsy interpretation and miscarriages of justice due to a lack of scientific verification in expert witness testimony. A method to examine the mechanisms of skeletal trauma, specifically skull fracture, in children would be beneficial in providing a solid biomechanical foundation to the forensic investigators in these child abuse cases. Finite element (FE) computational modeling techniques can be used to simulate failure of materials, including biological materials such as bone. However the efficacy of these methods has not been thoroughly tested against a well-defined experimental dataset, particularly for the pediatric population. The specific aims of this study were: (1)To determine appropriate constitutive laws and material properties for the piglet skull and suture, (2) To predict skull fracture patterns in a piglet model using FE methods, and (3) To analyze the sensitivity and robustness of these FE techniques for reliable biomechanical and forensic analysis. Results highlight the ability of macro-scale blunt impact computational models to predict fracture initiation sites and the role of computational models in guiding future experimental work

Nucleic Acid Carriers Based on Precise Polymer Conjugates

Polymer polydispersity, random conjugation of functional groups, and poorly understood structure–activity relationships have constantly hampered progress in the development of nucleic acid carriers. This review focuses on the synthetic concepts for the generation of precise polymers, site-specific conjugation strategies, and multifunctional conjugates for nucleic acid transport. Dendrimers, defined peptide carriers, sequence-defined polyamidoamines assembled by solid-phase supported synthesis, and precise lipopeptides or lipopolymers have been characterized for pDNA and siRNA delivery. Conjugation techniques such as click chemistries and peptide ligation are available for conjugating polymers with functional transport elements such as targeting or shielding domains and for direct covalent modification of therapeutic nucleic acids in a site-specific mode

New Sequence-Defined Polyaminoamides with Tailored Endosomolytic Properties for Plasmid DNA Delivery

Heterogeneity of polymeric carriers is one of the most elusive obstacles in the development of nonviral gene delivery systems, concealing interaction mechanisms and limiting the use of structure–activity relationship studies. In this report, novel sequence-defined polyaminoamides, prepared by solid-phase assisted synthesis, were used to establish first structure–activity relationships for polymer-based plasmid DNA delivery. By combining a cationic building block with hydrophobic modifications and bioreversible disulfide cross-linking sites, transfection polymers with tailored lytic and DNA binding properties were designed. These polymers demonstrated clear correlation between structure and performance in lysis and DNA binding assays. In vitro studies showed negligible toxicity and highly efficient gene transfer, demonstrating the potential of this platform in the fast, combinatorial development of new transfection polymers

A flow-oriented process model of social media services use

While social media has been a popular subject to extant research, we know little about the conditions and the flows of action of social media use, including staying, discontinuance, and switching behavior. This makes it difficult to understand platform choices and usage patterns of social media services. Based on a flow-oriented theoretical approach, we conduct an exploratory multiple case study of five popular social media services. We conceptualize a multidimensional perspective of social media use behavior. We identify four flows of action – “adjusting”, “coextending”, “fading out”, and “intensifying” – and develop a flow-oriented process model of social media service use. Our results help to understand the wide spectrum of use behavior and motives in social media services and provide new avenues to future research. Furthermore, we provide platform providers with insights to better understand the dynamics of social media services