> "fan" in buy and sell in Kelowna Get an alert with the newest ads for "fan" in Kelowna.The requested URL /scielo.php?script=sci_arttext&pid=S0103-50532012000100022 was not found on this server. DOI: *E-mail: mwinnik@chem.utoronto.ca.AbstractIsothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659–8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQV = δq/dV) of direct and reverse calorimetry titrations.

Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal–ligand pairs studied. Supporting InformationThe Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpcb.5b09202.General derivation procedure and numerical integration approach to evaluate the DBM. Supporting Tables with correlation matrices. View: ACS ActiveView PDF | Volume 50, Issue 1, 13 February 2013, Pages 219–228 Fine tuning of the coordination environments and magnetic properties of first row transition metal ions with 5-methylisophthalate and 2,2′-bipyridine/phenanthroline Received 9 August 2012, Accepted 29 October 2012, Available online 19 November 2012Twelve coordination compounds of Mn2+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+, with mixed organic ligands 5-methylisophthalic acid, 2,2′-bipyridine or phenanthroline, have been hydrothermally synthesised and characterised.

The magnetic properties of the Mn2+, Co2+, Ni2+ and Cu2+ compounds have been investigated. Structure analysis shows that the assemblies with a bridging ligand possessing a smaller methyl group (compared to the tert-butyl group) afford coordination compounds containing multinuclear metal centres and structures of higher dimension. air duct cleaning owatonna mnThe result shows that the structures and properties of the metal–organic materials can be finely tuned by the substituent on the organic bridging ligands.jual airbrush cleaning potGraphical abstractSubstituent on organic bridging ligand can be used as a regulator to adjust the structure and property of metal-organic materials.3q air purifierHighlights► The substituent on the organic bridging ligand is used to adjust the structure.

► The magnetic property can also be finely tuned by the substituent. ► 5-Methylisophthalate can distinguish metal ions with slight difference in diameters.Skip over navigation to the main contentDocument PreviewPreparation of Ag^sub 2^SO^sub 3^ sub-microparticles with high visible-light photocatalytic activityOpen with your PDF readerMetal–organic frameworks (MOFs) feature a great possibility for a broad spectrum of applications. Hollow MOF structures with tunable porosity and multifunctionality at the nanoscale with beneficial properties are desired as hosts for catalytically active species. Herein, we demonstrate the formation of well-defined hollow Zn/Co-based zeolitic imidazolate frameworks (ZIFs) by use of epitaxial growth of Zn-MOF (ZIF-8) on preformed Co-MOF (ZIF-67) nanocrystals that involve in situ self-sacrifice/excavation of the Co-MOF. Moreover, any type of metal nanoparticles can be accommodated in Zn/Co-ZIF shells to generate yolk–shell metal@ZIF structures. Transmission electron microscopy and tomography studies revealed the inclusion of these nanoparticles within hollow Zn/Co-ZIF with dominance of the Zn-MOF as shell.

Our findings lead to a generalization of such hollow systems that are working effectively to other types of ZIFs.Since their inception in the 1920s aluminium based adjuvants (ABA) have remained the predominantly used adjuvants in human vaccinations1. ABA are aluminium salts dispersed in water to form heterogeneous suspensions or gels, of hydrated colloid particles that consist of micron-sized aggregates of 1–20 μm with primary particles in the nano-size range2,3,4. Aluminium oxyhydroxide (AlO(OH)) adjuvants such as the licensed ABA Alhydrogel® (Brenntag Biosector, Denmark)5 are the most commonly used manufactured ABA in clinical vaccinations. AlO(OH)-based adjuvants are principally used owing to being the most well-defined and consistent of the clinically approved ABA and in their ability to adsorb negatively charged protein antigens from aqueous solutions at physiological pH2.When formulated in vaccine preparations, ABA both potentiate the efficacy of weak antigens and shape the resultant immune response6.

Use of antigen only often results in weak immunopotentiation and little or no antibody production7. Whilst the efficacy of ABA is undisputed, a consensus is yet to be reached upon their biological activities in vivo. ABA including aluminium hydroxide preparations are used in vaccinating against diphtheria, hepatitis A and B and against human papilloma virus (HPV) to prevent cervical cancers6,7. An ever intensifying research effort is currently underway to explain the observed adjuvanticity of ABA with several studies highlighting their physicochemical properties as a key determinant. Interestingly it has been shown that nanoparticles of aluminium hydroxide of ca 200 nm elicit more potent adjuvant activities in an in vivo model of murine adjuvanticity, than larger particles in the micron-size range9. The increased adjuvanticity of aluminium hydroxide nanoparticles was explained by their greater ease of uptake by dendritic antigen presenting cells (APCs)9.Variation of the physicochemical properties of AlO(OH)-based adjuvants via engineering particles with defined shape, size and morphology characteristics has been used in studying their immunopotentiating properties10.

Recent research by Sun and co-workers (2013) showed that the design of ordered rod-like AlO(OH) nanoparticles with higher crystallinity resulted in greater cellular uptake of the antigen and increased IL-1β production10. Interestingly, increased production of IL-12 and IL-6 was observed in bone marrow-derived dendritic cells (BMDCs) for the engineered AlO(OH) nanorods, the former being a known polariser of a Th1 response7. Therefore alteration of the physicochemical properties of aluminium hydroxide based adjuvants alone has been shown to shape their immunostimulatory properties both in vivo and in vitro9,10.Surprisingly, little experimental information has eluded to the potential cellular uptake of ABA or any compartmentalisation of ABA, inside the cell3,11,12,13,14,15. This has been suggested to be critical for the activation and assembly of the Nalp3 inflammasome, driving pro-inflammatory immune responses via secretion of mature interleukin IL-1β and IL-18 cleaved from the prointerleukins by actvated caspase-116,17.

Ultrastructural investigations paired with X-ray microanalysis have previously been used to successfully confirm the presence of aluminium in the skin13.Aluminium hydroxide granulomas from excised subcutaneous nodules were identified in three children ranging in age from 18 to 36 months following injection of a diphtheria, tetanus and pertussis vaccine, adjuvanted with aluminium hydroxide13. Whilst aluminium was identified in the skin the aluminium signal measured was not confined to any intracellular environment and hence evidence of intracellular aluminium was neither inferred by the authors nor could it be established unequivocally13.Further X-ray based methods have used particle-induced X-ray emission (PIXE) to identify aluminium in quadriceps muscle of Cynomolgus monkeys, following intramuscular administration of a Diphtheria-tetanus vaccine containing 0.6 mg/mL of either AlO(OH) or aluminium hydroxyphosphate (AlPO4) based adjuvants14. Increases in the aluminium concentration were found at a muscular level over scanned areas of 1 mm2 in the injection site, with marked increases identified in muscular lesions following 3 and 6 months post-injection14.

No results were included however to show that aluminium was localised within cells.A study by Rimaniol and co-workers (2004) demonstrated the presence of crystalline inclusions in macrophages exposed to 2 μg/mL aluminium oxyhydroxide (AlO(OH)) adjuvant via transmission electron microscopy (TEM)15. Electron micrographs revealed electron dense material scattered throughout macrophages. In spite of the observations of electron dense material in macrophages, no direct evidence was provided to confirm that those inclusions identified contained particulate AlO(OH)15. A more recent study by Lu & HogenEsch (2013) highlighted the presence of an ABA (Rehydragel™ HPA, USA) in murine macrophages using morin (2,3,4,5,7-pentahydroxy- flavone) staining11.An earlier investigation using the same method found ABA internalised in epithelioid macrophages and multinucleated giant cells in rhesus macaque skin sections12. No autofluorescence controls were shown in either paper however and the influences of the protein antigens alone were not addressed11,12.

Morin is also known to bind to magnesium (Mg2+) and calcium (Ca2+) ions to produce false positives18. A hydrochloric acid pre-rinse, prior to staining is frequently used to account for such. The resultant acidity however, is likely to promote the formation of soluble Al3+ increasing the likelihood of the dissolution of aluminium bound in tissue and its possible migration throughout the tissue19.Investigations monitoring the potential cellular uptake of ABA have preferentially labelled the adsorbed protein antigen (often ovalbumin (OVA)) with the amine-reactive derivative of the fluorescein dye, fluorescein isothiocyanate (FITC)9,10,20,21. Following adsorption of an ABA with FITC-labelled OVA, the presence of the adjuvant has been inferred intracellularly in cultured DC-lines by use of confocal microscopy20,21, fluorescence microscopy9 and flow cytometry10,20,21. Whilst the presence of the OVA protein antigen has been observed intracellularly within APCs9,20,21, whether the adsorbed ABA is internalised or not remains to be determined as the use of FITC only allows for the identification of internalised antigen.

Pre-labelling AlO(OH) adjuvants with FITC via the use of pre-incubation with organic moieties10 may also result in changes to the surface of the particulates as well as modifications to their hydroxyl functionality and size. This may in turn affect their uptake as the variation of such physicochemical properties of ABA has been shown to dramatically affect their cellular uptake8,9,10. Furthermore, potential modifications to the endocytic/phagocytic pathways of internalisation following conjugation of the ABA to FITC-OVA cannot be ruled out.Use of AlO(OH) (Alhydrogel, Brenntag) formulated with the chimaeric Ealpha green fluorescent protein (EαGFP) demonstrated an increase in antigen uptake compared to uptake of EαGFP alone via the detection of GFP using flow cytometry22. As with the use of FITC only the presence of the antigen could be inferred inside the cell of which the authors summarised that ABA provide an enhanced delivery mechanism of the antigen only whilst not addressing potential uptake of the adjuvant by dendritic cells (DCs)22.

Additional studies have supported these conclusions with crystals of the ABA being suggested to not enter the cell and rather aid in the transport of the antigen across DC membranes with activation of the Nalp3 inflammasome being dispensable for triggering subsequent immune responses23.Few if any studies within the literature have therefore shown the direct monitoring of the intracellular ABA content of various immune cells and a consensus upon the biological activates of ABA has yet to be reached16,17. Herein we report for the first time the unequivocal identification of intracellular AlO(OH) particles both for a clinically approved and an experimental AlO(OH)-based adjuvant in a monocytic T-helper 1 (THP-1) cell line. Positive identification of particulate ABA was observed intracellularly by use of the planar tridentate ligand lumogallion [4-chloro-3-(2,4-dihydroxyphenylazo)-2-hydroxybenzene-1-sulphonic acid] as a fluorescent molecular probe for aluminium24.Lumogallion is commonly used to detect the presence of aluminium at low concentrations in natural waters with a limit of detection of ca 2 nM25 and has been used extensively for the identification of the metal ion in plant roots26,27.