Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday

Dendrimers have firmly established their space in the macromolecular field since their first discovery in 1978. These monodispersed and hyperbranched macromolecules present unique properties with demonstrated potential in varied scientific disciplines. Dr. Donald A Tomalia is one of the pioneers in this area whose name is synonym for polyamidoamine (PAMAM) dendrimers, one of the most extensively investigated macromolecular architectures. In this monograph, his colleagues and friends celebrate Don’s achievements and contributions to the field, on the occasion of his 80th birthday in 2018, which also coincides with the 40th anniversary of the first report on dendrimers. It provides the reader with excellent reviews on different aspects of dendritic architectures, followed by research articles that explore the state-of-the-art in synthesis, properties and varied applications, including in biology. Collectively, it provides scientists just beginning their careers, as well as firmly established ones, with the pulse of the field and inspiration to continue to explore these intriguing macromolecules

Dendrimers as anti-inflammatory agents

Dendrímeros constituem uma classe intrigante de macromoléculas que apresentam aplicações em diversas áreas incluindo biologia. Essas macromoléculas extremamente ramificadas com esqueleto planejado e grupos de superfície foram extensivamente investigadas como nanotransportadores de genes e de fármacos, por encapsulamento molecular ou conjugação covalente. Dendrímeros têm proporcionado uma plataforma excelente de desenvolvimento nanoconjugados multivalentes e multifuncionais incorporando uma variedade de grupos funcionais, incluindo fármacos que são conhecidos por atuarem agentes antiinflamatórios. Recentemente, os dendrímeros mostraram propriedades antiinflamatórias. Esta inesperada e intrigante descoberta tem proporcionado um impulso adicional no planejamento de novos agente farmacêuticos ativos. Nesta revisão, nós destacamos alguns dos desenvolvimentos recentes no campo dos dendrímeros como agentes antiinflamatórios em nanoescala.Dendrimers constitute an intriguing class of macromolecules which find applications in a variety of areas including biology. These hyperbranched macromolecules with tailored backbone and surface groups have been extensively investigated as nanocarriers for gene and drug delivery, by molecular encapsulation or covalent conjugation. Dendrimers have provided an excellent platform to develop multivalent and multifunctional nanoconjugates incorporating a variety of functional groups including drugs which are known to be anti-inflammatory agents. Recently, dendrimers have been shown to possess anti-inflammatory properties themselves. This unexpected and intriguing discovery has provided an additional impetus in designing novel active pharmaceutical agents. In this review, we highlight some of the recent developments in the field of dendrimers as nanoscale anti-inflammatory agents

Probability Analysis of a Complex System Working in a Sugar Mill with Repair Equipment Failure and Correlated Life Time

The aim of this paper is to present a reliability analysis of a complex (SJP) system in a sugar mill with the assumption that repair equipment may also fail during the repair. This paper considers the analysis of a three-unit system with one big unit and two small identical units of a SJP System in a sugar mill. Failure and Repair times of each unit are assumed to be correlated. Using regenerative point technique various reliability characteristics are obtained which are useful to system designers and industrial managers. Graphical behaviors of MTSF and profit function have also been studied

Profit Analysis of Non-Identical Parallel System with Two Types of Failure Using Discrete Distribution

This paper has analyzed the two non-identical operative parallel systems considering two units (automatic and manual one) by using regenerative point technique. For theautomatic unit, the concept of inspection policy has been introduced to detect the kind of failures (major or minor) before being repaired by some repair mechanism. Butthe manual unit is free from such inspection policy. Various important measures of reliability i.e MTSF, steady-state availability, a busy period of repairman and inspector,profit function has been evaluated by designing a model for the system and using discrete distribution & regenerative point techniques. Profit function and MTSF are also analyzed graphically

Cerebral tissue pO2 response to stimulation is preserved with age in awake mice

Published in final edited form as: Neurosci Lett. 2019 April 23; 699: 160–166. doi:10.1016/j.neulet.2019.02.007.Compromised oxygen supply to cerebral tissue could be an important mechanism contributing to age-related cognition decline. We recently showed in awake mice that resting cerebral tissue pO2 decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO2 response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO2 response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO2, the amplitude of the tissue pO2 response to stimulation is well preserved with age. However, the response dynamics are altered towards a slower response with reduced post-stimulus undershoot in older ages, possibly due to stiffer vessel wall among other factors. An estimation of the net oxygen consumption rate using a modified Krogh model suggests that the O2 overshoot during stimulation may be necessary to secure a higher capillary O2 delivery to the tissue proportional to increased CMRO2 to maintain the capillary tissue pO2. It was observed that the coupling between the CMRO2 and capillary O2 delivery is preserved with age.Accepted manuscrip

Alkyne-Azide “click” chemistry in designing nanocarriers for applications in biology

The alkyne-azide cycloaddition, popularly known as the "click" reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include high efficiency, and adaptability to the environment in which the desired covalent linking of the alkyne and azide terminated moieties needs to be carried out. The efficient delivery of active pharmaceutical agents to specific organelles, employing nanocarriers developed through the use of "click" chemistry, constitutes a continuing topical area of research. In this review, we highlight important contributions click chemistry has made in the design of macromolecule-based nanomaterials for therapeutic intervention in mitochondria and lipid droplets

Cerebral tissue pO2 response to treadmill exercise in awake mice

ABSTRACT: We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO2 response to forced treadmill exercise in awake mice. To our knowledge, this is the first study performing both direct measure of brain tissue pO2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5–15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease

Multifaceted ligand design facilitates chemical- or peptide-mediated linking of hollow gold nanoshells with tuned interparticle distance, interference and cytotoxicities

ABSTRACT: We report a versatile methodology to covalently link hollow gold nanoshells (HAuNS) through modular design of multi-tasking ligands and bio-adaptable chemistry. The biocompatible ligand composition includes strategically placed two polyethylene glycol (PEG) chains, protected thiol-terminated tetraethylene glycol, and a reactive functional group, on a core. HAuNS are functionalized through an in situ one-pot deprotection/thiol-Au binding. The ligand-functionalized HAuNS with surface exposed COOH or OH entities are employed in constructing linked-HAuNS conjugated through a short chemical- or a longer bio-spacer (GPLGVRG peptide), in which (i) the length of the PEG chains plays an important role in minimizing oligomerization during covalent linking of HAuNS; (ii) inter-particle distance and interference of HAuNS surface plasmon resonance are regulated through chemical/peptide junctions, with UV-Vis-NIR absorption maxima red-shifted in chem-linked HAuNS; and (iii) chem-linked HAuNS-to-monomer conversion leads to amplification of the photoacoustic signal. Ligand stabilized monomeric and linked-HAuNS are less cytotoxic than citrate protected HAuNS. The synthetic tools and facile chemistry described here provide opportunities in designing linked metal nanoparticles for broad applications in biology

Fabricating water dispersible superparamagnetic iron oxide nanoparticles for biomedical applications through ligand exchange and direct conjugation

Stable superparamagnetic iron oxide nanoparticles (SPIONs), which can be easily dispersed in an aqueous medium and exhibit high magnetic relaxivities, are ideal candidates for biomedical applications including contrast agents for magnetic resonance imaging. We describe a versatile methodology to render water dispersibility to SPIONs using tetraethylene glycol (TEG)-based phosphonate ligands, which are easily introduced onto SPIONs by either a ligand exchange process of surface-anchored oleic-acid (OA) molecules or via direct conjugation. Both protocols confer good colloidal stability to SPIONs at different NaCl concentrations. A detailed characterization of functionalized SPIONs suggests that the ligand exchange method leads to nanoparticles with better magnetic properties but higher toxicity and cell death, than the direct conjugation methodology

Compromised microvascular oxygen delivery increases brain tissue vulnerability with age

Despite the possible role of impaired cerebral tissue oxygenation in age-related cognition decline, much is still unknown about the changes in brain tissue pO2 with age. Using a detailed investigation of the age-related changes in cerebral tissue oxygenation in the barrel cortex of healthy, awake aged mice, we demonstrate decreased arteriolar and tissue pO2 with age. These changes are exacerbated after middle-age. We further uncovered evidence of the presence of hypoxic micro-pockets in the cortex of awake old mice. Our data suggests that from young to middle-age, a well-regulated capillary oxygen supply maintains the oxygen availability in cerebral tissue, despite decreased tissue pO2 next to arterioles. After middle-age, due to decreased hematocrit, reduced capillary density and higher capillary transit time heterogeneity, the capillary network fails to compensate for larger decreases in arterial pO2. The substantial decrease in brain tissue pO2, and the presence of hypoxic micro-pockets after middle-age are of significant importance, as these factors may be related to cognitive decline in elderly people