Supplemental Material - Can spatial patterns mitigate the urban heat island effect? Evidence from German metropolitan regions

Supplemental Material for Can spatial patterns mitigate the urban heat island effect? Evidence from German metropolitan regions by Wenzheng Li, and Stephan Schmidt in Environment and Planning B: Urban Analytics and City Science.</p

2012 MoodlePosium

I attended and presented at the 2012 MoodlePosium held at the University of Canberra, 22nd and 23rd of November, 2012. I was doing some contract work with Brightcookie at the time and also heavily promoting the Streamfolio application. The presentation was a joint exercise with Leo Gaggl and we spoke of the many and varied ways that POV and body wearable video could work within the learning management context ie. Moodle and Mahara

Specific Adhesion of Carbohydrate Hydrogel Particles in Competition with Multivalent Inhibitors Evaluated by AFM

Synthetic glycooligomers have emerged as valuable analogues for multivalent glycan structures in nature. These multivalent carbohydrates bind to specific receptors and play a key role in biological processes. In this work, we investigate the specific interaction between mannose ligand presenting soft colloidal probes (SCPs) attached to an atomic force microscope (AFM) cantilever and a Concanavalin A (ConA) receptor surface in the presence of competing glycooligomer ligands. We studied the SCP–ConA adhesion energy via the JKR approach and AFM pull-off experiments in combination with optical microscopy allowing for simultaneous determination of the contact area between SCP and ConA surface. We varied the contact time, loading rate and loading force and measured the resulting mannose/ConA interaction. The average adhesion energy per mannose ligand on the probe was 5 kJ/mol, suggesting that a fraction of mannose ligands presented on the SCP bound to the receptor surface. Adhesion measurements via competitive binding of the SCP in the presence of multivalent glycooligomer ligands did not indicate an influence of their multivalency on the glycooligomer displacement from the ConA surface. The absence of this “multivalency effect” indicates that glycooligomers and ConA do not associate via chelate complexes and shows that steric shielding by the glycooligomers does not slow their displacement upon competitive binding of a ligand presenting surface. These results highlight the high reversibility of carbohydrate–surface interactions, which could be an essential feature of recognition processes on the cell surface

Metal-Mediated Molecular Self-Healing in Histidine-Rich Mussel Peptides

Mussels withstand high-energy wave impacts in rocky seashore habitats by fastening tightly to surfaces with tough and self-healing proteinaceous fibers called byssal threads. Thread mechanical behavior is believed to arise from reversibly breakable metal coordination cross-links embedded in histidine-rich protein domains (HRDs) in the principle load-bearing proteins comprising the fibrous thread core. In order to investigate HRD behavior at the molecular level, we have synthesized a histidine-rich peptide derived from mussel proteins (His₅-bys) and studied its reversible adhesive self-interaction in the presence and absence of metal ions using PEG-based soft-colloidal probes (SCPs). Adhesion energies of greater than 0.3 mJ/m² were measured in the presence of metal ions, and the stiffness of the modified SCPs exhibited a 3-fold increase, whereas no adhesion was observed in the absence of metals. Raman spectroscopy confirmed the presence of metal-coordination via histidine residues by the peptide–supporting the role of His-metal complexes in the mechanical behavior of the byssus

Sequence-Controlled High Molecular Weight Glyco(oligoamide)–PEG Multiblock Copolymers as Ligands and Inhibitors in Lectin Binding

A synthesis toward sequence-controlled multiblock glycopolymers, presenting a mannopyranoside (Man) glyco­(oligoamide) block followed by a poly­(ethylene glycol) (PEG) (<i>M̅</i>_n of 6 kDa) block, is shown. Therefore, monodisperse and sequence-defined glyco­(oligoamide) macromonomers derived from solid phase synthesis (SPS) are polymerized with dithiol-functionalized PEG via thiol–ene coupling (TEC) in a step-growth fashion. For the polymerization, a novel building block introducing a norbornene moiety is developed which is used for end-functionalization of the glyco­(oligoamide) macromonomers. As a highly reactive alkene moiety in photoinduced TEC, this gives access to <i>X̅</i>_n of up to 45. A total of 12 glyco­(oligoamide)–PEG multiblock copolymers with maximum <i>M̅</i>_n of 200 kDa are obtained and subjected to a series of purification steps decreasing overall dispersity. In different binding studies toward model lectin Concanavalin A, despite their high number of Man ligands, we see rather weak binding of glycopolymers that we attribute to the introduction of higher molecular weight PEG blocks

Multivalent Binding of Precision Glycooligomers on Soft Glycocalyx Mimicking Hydrogels

We present a synthetic approach toward soft, glycooligomer-functionalized microgel particles mimicking carbohydrate presenting cell surfaces and analyze their specific binding to a model lectin (Concanavalin A, ConA). Focusing on multivalent presentation, a series of sequence-controlled glycooligomers with varying spacing and number of mannose units was synthesized and analyzed for the resulting glycooligomer–ConA affinity. Both direct binding and inhibition studies show a higher affinity with increasing the number of sugar moieties, but they level off for higher valent systems, indicating steric hindrance. Furthermore, the results suggest that increasing the scaffold length tends to decrease binding due to entropic repulsion, which could be compensated by larger scaffolds able to address multiple ConA binding sites. These findings were consistent in all assays (adhesion, fluorescence, and ITC) regardless of binding partner immobilization, demonstrating that flexible ligands exert similar binding modes in solution and when attached to polymer networks, which is relevant for designing glyco-functionalized materials

Identification and Quantification of Protein Adducts Formed by Metabolites of 1‑Methoxy-3-indolylmethyl Glucosinolate <i>in Vitro</i> and in Mouse Models

1-Methoxy-3-indolylmethyl (1-MIM) glucosinolate (GLS) occurring in cabbage, broccoli, and other cruciferous plants is a potent mutagen requiring metabolic activation by myrosinase present in plant cells and intestinal bacteria. We previously reported that 1-MIM-GLS and its alcoholic breakdown product 1-MIM-OH, which requires additional activation by sulfotransferases, form DNA adducts in mice. In the present study, the formation of protein adducts was investigated. First, two major adducts obtained after incubation of individual amino acids, serum albumin, or hemoglobin with 1-MIM-GLS in the presence of myrosinase were identified as τ<i>N</i>-(1-MIM)-His and π<i>N</i>-(1-MIM)-His using MS and NMR spectroscopy. After the development of a specific detection method using isotope-dilution UPLC-ESI-MS/MS, adduct formation was confirmed in mice after oral treatment with 1-MIM-GLS. Adduct levels were highest in the cecum and colon, somewhat lower in serum albumin and the liver, and also readily detectable in the lung and hemoglobin. On the contrary, oral treatment with 1-MIM-OH produced the highest adduct levels in the liver. The higher ratio of albumin to hemoglobin adducts in 1-MIM-OH- compared to 1-MIM-GLS-treated animals (8.1 versus 3.5) suggests that in 1-MIM-OH-treated animals albumin adducts were produced mostly in the liver, the site of albumin synthesis. The formation of adducts was approximately linear over a range of single oral doses from 20 to 600 μmol/kg body mass. Repeated oral administration of 1-MIM-OH (up to 40 treatments, thrice per week) led to continuous accumulation of hemoglobin adducts, whereas the level of serum albumin adducts remained rather constant, which reflects the different turnover rates of these proteins (<i>t</i>_1/2 nearly 1.9 d for serum albumin and 25 d for hemoglobin in the mouse). Accumulation of adducts was also noticed in the lung. Adduct levels were higher, but their accumulation was weaker in the liver and kidney. The method developed will be useful to assess the exposure of humans to reactive metabolites formed from 1-MIM-GLS present in many foods

Magnetic Porous Sugar-Functionalized PEG Microgels for Efficient Isolation and Removal of Bacteria from Solution

Here, we present a new microparticle system for the selective detection and magnetic removal of bacteria from contaminated solutions. The novelty of this system lies in the combination of a biocompatible scaffold reducing unspecific interactions with high capacity for bacteria binding. We apply highly porous poly­(ethylene glycol) (PEG) microparticles and functionalize them, introducing both sugar ligands for specific bacteria targeting and cationic moieties for electrostatic loading of superparamagnetic iron oxide nanoparticles. The resulting magnetic, porous, sugar-functionalized (MaPoS) PEG microgels are able to selectively bind and discriminate between different strains of bacteria Escherichia coli. Furthermore, they allow for a highly efficient removal of bacteria from solution as their increased surface area can bind three times more bacteria than nonporous particles. All in all, MaPoS particles represent a novel generation of magnetic beads introducing for the first time a porous, biocompatible and easy to functionalize scaffold and show great potential for various biotechnological applications

Supplement_for_TOLERATE_manuscript – Supplemental material for Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE)

<p>Supplemental material, Supplement_for_TOLERATE_manuscript for Incidence and mitigation of gastrointestinal events in patients with relapsing–remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE) by Ralf Gold, Eugen Schlegel, Birte Elias-Hamp, Christian Albert, Stephan Schmidt, Björn Tackenberg, James Xiao, Tom Schaak and Hans Christian Salmen in Therapeutic Advances in Neurological Disorders</p

Carbohydrate-Lectin Recognition of Sequence-Defined Heteromultivalent Glycooligomers

Multivalency as a key principle in nature has been successfully adopted for the design and synthesis of artificial glycoligands by attaching multiple copies of monosaccharides to a synthetic scaffold. Besides their potential in various applied areas, e.g. as antiviral drugs, for the vaccine development and as novel biosensors, such glycomimetics also allow for a deeper understanding of the fundamental aspects of multivalent binding of both artificial and natural ligands. However, most glycomimetics so far neglect the purposeful arranged heterogeneity of their natural counterparts, thus limiting more detailed insights into the design and synthesis of novel glycomimetics. Therefore, this work presents the synthesis of monodisperse glycooligomers carrying different sugar ligands at well-defined positions along the backbone using for the first time sequential click chemistry and stepwise assembly of functional building blocks on solid support. This approach allows for straightforward access to sequence-defined, multivalent glycooligomers with full control over number, spacing, position, and type of sugar ligand. We demonstrate the synthesis of a set of heteromultivalent oligomers presenting mannose, galactose, and glucose residues. All heteromultivalent structures show surprisingly high affinities toward Concanavalin A lectin receptor in comparison to their homomultivalent analogues presenting the same number of binding ligands. Detailed studies of the ligand/receptor interaction using STD-NMR and 2fFCS indeed indicate a change in binding mechanism for trivalent glycooligomers presenting mannose or combinations of mannose and galactose residues. We find that galactose residues do not participate in the binding to the receptor, but they promote steric shielding of the heteromultivalent glycoligands and thus result in an overall increase in affinity. Furthermore, the introduction of nonbinding ligands seems to suppress receptor clustering of multivalent ligands. Overall these results support the importance of heteromultivalency specifically for the design of novel glycoligands and help to promote a fundamental understanding of multivalent binding modes