PHENOMENON OF THE AMERICAN DREAM IN PERCIVAL EVERETT’S NOVELS

Abstract.The article deals with two mostly well-known novels American Desert and I Am Not Sidney Poitierby Percival Everett. Nowadays he is one of the most accomplished and prolific American writers and belongs to a “new” generation of black writers. In his novels the author addresses the phenomenon of the American Dream which is one of the most widespread themes in the literature of the USA in the XX-XXI centuries. The authors of the article come to the conclusion that the novels are based on the same plot structure demonstrating the compelling impact of this phenomenon on the protagonists’ lives. The main aim of appealing to the phenomenon is to present author’s views upon this question, to give the way of its new interpretation, to discuss the related problems of American society. The writer also presents the transformation of the phenomenon of the American Dream into American tragedy. This way ofinterpretation is based on postmodernist aesthetics mostly.Key words: Percival Everett, American Dream, American way of life, American tragedy, self-made pe

TRADITIONS OF PURITANISM IN THE MID-20 TH CENTURY AMERICAN NOVEL: LEGACY, DIALOGUE AND DEBATE

Abstract. The paper explores the evolution and transformation of Puritan ethical and moral principles in themid-20 th century American literature as represented by novels of John Cheever and John Updike providing both idealized and revisionist insight into traditional Puritan values that form the foundation of American culture. The key tenets of Puritanism underwent profound rethinking and revision throughout the history of American literature. The interpretation of the worldly asceticism concept in the new historical context is discussed as the key component in the revision of Puritan legacy. The analysis of alternative perspectives on desacralization of daily life in the works of heever and Updike reveals different paths they take for a continued dialogue with the tradition. John Cheever is nostalgic about the long lost simplicity and meaning of the bygone life, while John Updike turns to Karl Barth’s theology to prove the moral ineptitude of worldly asceticism in the modern world.Key words: tradition, Puritanism, worldly asceticism, John Updike, John Cheever

Nanoparticles of Block Ionomer Complexes from Double Hydrophilic Poly(acrylic acid)-b-poly(ethylene oxide)-b-poly(acrylic acid) Triblock Copolymer and Oppositely Charged Surfactant

The novel water-dispersible nanoparticles from the double hydrophilic poly(acrylic acid)-b-poly(ethylene oxide)-b-poly(acrylic acid) (PAA-b-PEO-b-PAA) triblock copolymer and oppositely charged surfactant dodecyltrimethyl ammonium bromide (DTAB) were prepared by mixing the individual aqueous solutions. The structure of the nanoparticles was investigated as a function of the degree of neutralization (DN) by turbidimetry, dynamic light scattering (DSL),ζ-potential measurement, and atomic force microscope (AFM). The neutralization of the anionic PAA blocks with cationic DTAB accompanied with the hydrophobic interaction of alkyl tails of DTAB led to formation of core–shell nanoparticles with the core of the DTAB neutralized PAA blocks and the shell of the looped PEO blocks. The water-dispersible nanoparticles with negative ζ-potential were obtained over the DN range from 0.4 to 2.0 and their sizes depended on the DN. The looped PEO blocks hindered the further neutralization of the PAA blocks with cationic DTAB, resulting in existence of some negative charged PAA-b-PEO-b-PAA backbones even when DN > 1.0. The spherical and ellipsoidal nature of these nanoparticles was observed with AFM

Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells

A new family of nanoscale materials on the basis of dispersed networks of cross-linked ionic and nonionic hydrophilic polymers is being developed. One example is the nanosized cationic network of cross-linked poly(ethylene oxide) (PEO) and polyethyleneimine (PEI), PEO-cl-PEI nanogel. Interaction of anionic amphiphilic molecules or oligonucleotides with PEO-cl-PEI results in formation of nanocomposite materials in which the hydrophobic regions from polyion-complexes are joined by the hydrophilic PEO chains. Formation of polyion-complexes leads to the collapse of the dispersed gel particles. However, the complexes form stable aqueous dispersions due to the stabilizing effect of the PEO chain. These systems allow for immobilization of negatively charged biologically active compounds such as retinoic acid, indomethacin and oligonucleotides (bound to polycation chains) or hydrophobic molecules (incorporated into nonpolar regions of polyion–surfactant complexes). The nanogel particles carrying biological active compounds have been modified with polypeptide ligands to enhance receptor-mediated delivery. Efficient cellular uptake and intracellular release of oligonucleotides immobilized in PEO-cl-PEI nanogel have been demonstrated. Antisense activity of an oligonucleotide in a cell model was elevated as a result of formulation of oligonucleotide with the nanogel. This delivery system has a potential of enhancing oral and brain bioavailability of oligonucleotides as demonstrated using polarized epithelial and brain microvessel endothelial cell monolayers

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory\u27s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery

Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity and Staphylococcus Aureus Biofilm Clearance

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm persistence. To shift monocyte metabolism in vivo and reprogram cells to a pro-inflammatory state, a nanoparticle approach was utilized to deliver the OxPhos inhibitor oligomycin to monocytes. Using a mouse model of S. aureus PJI, oligomycin nanoparticles were preferentially internalized by monocytes, which significantly reduced S. aureus biofilm burden by altering metabolism and promoting the pro-inflammatory properties of infiltrating monocytes as revealed by metabolomics and RT-qPCR, respectively. Injection of oligomycin alone had no effect on monocyte metabolism or biofilm burden, establishing that intracellular delivery of oligomycin is required to reprogram monocyte metabolic activity and that oligomycin lacks antibacterial activity against S. aureus biofilms. Remarkably, monocyte metabolic reprogramming with oligomycin nanoparticles was effective at clearing established biofilms in combination with systemic antibiotics. These findings suggest that metabolic reprogramming of biofilm-associated monocytes may represent a novel therapeutic approach for PJI

Nanoformulation of the Superoxide Dismutase Mimic, MnTnBuOE-2-PyP5+, Prevents its Acute Hypotensive Response

Scavenging superoxide (O2•-) via overexpression of superoxide dismutase (SOD) or administration of SOD mimics improves outcomes in multiple experimental models of human disease including cardiovascular disease, neurodegeneration, and cancer. While few SOD mimics have transitioned to clinical trials, MnTnBuOE-2-PyP5+ (BuOE), a manganese porphyrin SOD mimic, is currently in clinical trials as a radioprotector for cancer patients; thus, providing hope for the use of SOD mimics in the clinical setting. However, BuOE transiently alters cardiovascular function including a significant and precipitous decrease in blood pressure. To limit BuOE\u27s acute hypotensive action, we developed a mesoporous silica nanoparticle and lipid bilayer nanoformulation of BuOE (nanoBuOE) that allows for slow and sustained release of the drug. Herein, we tested the hypothesis that unlike native BuOE, nanoBuOE does not induce an acute hypotensive response, as the nanoformulation prevents BuOE from scavenging O2•- while the drug is still encapsulated in the formulation. We report that intact nanoBuOE does not effectively scavenge O2•-, whereas BuOE released from the nanoformulation does retain SOD-like activity. Further, in mice, native BuOE, but not nanoBuOE, rapidly, acutely, and significantly decreases blood pressure, as measured by radiotelemetry. To begin exploring the physiological mechanism by which native BuOE acutely decreases blood pressure, we recorded renal sympathetic nerve activity (RSNA) in rats. RSNA significantly decreased immediately following intravenous injection of BuOE, but not nanoBuOE. These data indicate that nanoformulation of BuOE, a SOD mimic currently in clinical trials in cancer patients, prevents BuOE\u27s negative side effects on blood pressure homeostasis

Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases

Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics is immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. From the Clinical Editor Many nervous system disorders remain unresolved clinical problems. In many cases, drug agents simply cannot cross the blood-brain barrier (BBB) into the nervous system. The advent of nanomedicines can enhance the delivery of biologically active molecules for targeted therapy and imaging. This review focused on the use of nanotechnology for degenerative, inflammatory, and infectious diseases in the nervous system

Nanocarriers for delivery of platinum anticancer drugs

Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs