Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ~80% of MCC. The MCV large tumor ...(LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma protein-binding motif. We confirm here that YM155, a survivin suppressor, is cytotoxic to MCV-positive MCC cells in vitro at nanomolar levels. Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts. One MCV-positive MCC xenograft (MS-1) failed to significantly respond to YM155, which corresponds with in vitro dose-response activity. Combination treatment of YM155 with other chemotherapeutics resulted in additive but not synergistic cell killing of MCC cell lines in vitro. These results suggest that survivin targeting is a promising therapeutic approach for most but not all MCV-positive MCCs.
A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of ...superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe₂O₃ (maghemite) or Fe₃O₄ (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside.
Optimization is a mathematical tool developed in the early 1960's used to find the most efficient and feasible solutions to an engineering problem. It can be used to find ideal shapes and physical ...configurations, ideal structural designs, maximum energy efficiency, and many other desired goals of engineering. This book is intended for use in a first course on engineering design and optimization. Material for the text has evolved over a period of several years and is based on classroom presentations for an undergraduate core course on the principles of design. Virtually any problem for which certain parameters need to be determined to satisfy constraints can be formulated as a design optimization problem. The concepts and methods described in the text are quite general and applicable to all such formulations. Inasmuch, the range of application of the optimum design methodology is almost limitless, constrained only by the imagination and ingenuity of the user. The book describes the basic concepts and techniques with only a few simple applications. Once they are clearly understood, they can be applied to many other advanced applications that are discussed in the text. * Allows engineers involved in the design process to adapt optimum design concepts in their work using the material in the text * Basic concepts of optimality conditions and numerical methods are described with simple examples, making the material high teachable and learnable * Classroom-tested for many years to attain optimum pedagogical effectiveness
The objective of this study was to analyze the genetic relationships, using PCR-based ISSR markers, among 70 Indian flax (Linum usitatissimum L.) genotypes actively utilized in flax breeding ...programs. Twelve ISSR primers were used for the analysis yielding 136 loci, of which 87 were polymorphic. The average number of amplified loci and the average number of polymorphic loci per primer were 11.3 and 7.25, respectively, while the percent loci polymorphism ranged from 11.1 to 81.8 with an average of 63.9 across all the genotypes. The range of polymorphism information content scores was 0.03-0.49, with an average of 0.18. A dendrogram was generated based on the similarity matrix by the Unweighted Pair Group Method with Arithmetic Mean (UPGMA), wherein the flax genotypes were grouped in five clusters. The Jaccard's similarity coefficient among the genotypes ranged from 0.60 to 0.97. When the omega-3 alpha linolenic acid (ALA) contents of the individual genotypes were correlated with the clusters in the dendrogram, the high ALA containing genotypes were grouped in two clusters. This study identified SLS 50, Ayogi, and Sheetal to be the most diverse genotypes and suggested their use in breeding programs and for developing mapping populations.
Children and adolescents account for ~ 13% of total COVID-19 cases in the United States. However, little is known about the nature of the illness in children. The reopening of schools underlines the ...importance of understanding the epidemiology of pediatric COVID-19 infections. We sought to assess the clinical characteristics and outcomes in pediatric COVID-19 patients. We conducted a retrospective cross-sectional analysis of pediatric patients diagnosed with COVID-19 from healthcare organizations in the United States. The study outcomes (hospitalization, mechanical ventilation, critical care) were assessed using logistic regression. The subgroups of sex and race were compared after propensity score matching. Among 12,306 children with lab-confirmed COVID-19, 16.5% presented with respiratory symptoms (cough, dyspnea), 13.9% had gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). In the study cohort, the hospitalization frequency was 5.3%, with 17.6% needing critical care services and 4.1% requiring mechanical ventilation. Following propensity score matching, the risk of all outcomes was similar between males and females. Following propensity score matching, the risk of hospitalization was greater in non-Hispanic Black (RR 1.97 95% CI 1.49-2.61) and Hispanic children (RR 1.31 95% CI 1.03-1.78) compared with non-Hispanic Whites. In the pediatric population infected with COVID-19, a substantial proportion were hospitalized due to the illness and developed adverse clinical outcomes.
This comprehensive resource caters to system designers that are looking to incorporate lithium ion (li-ion) batteries in their applications. Detailed discussion of the various system considerations ...that must be addressed at the design stage to reduce the risk of failures in the field is presented. The book includes technical details of all state-of-the-art Li-on energy storage subsystems and their requirements, and provides a system designer a single resource detailing all of the common issues navigated when using Li-ion batteries to reduce the risk of field failures.The book details the various industry standards that are applicable to the subsystems of Li-ion energy storage systems and how the requirements of these standards may impact the design of their system. Checklists are included to help readers evaluate their own battery system designs and identify gaps in the designs that increase the risk of field failures. The book is packed with numerous examples of issues that have caused field failures and how a proper design/assembly process could have reduced the risk of these failures.
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