Multivalent glycan arrays

Glycan microarrays have become a powerful technology to study biological processes, such as cell–cell interaction, inflammation, and infections. Yet, several challenges, especially in multivalent display, remain. In this introductory lecture we discuss the state-of-the-art glycan microarray technology, with emphasis on novel approaches to access collections of pure glycans and their immobilization on surfaces. Future directions to mimic the natural glycan presentation on an array format, as well as in situ generation of combinatorial glycan collections, are discussed

On-chip neo-glycopeptide synthesis for multivalent glycan presentation

Single glycan-protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser-based array synthesis technology allows for flexible and rapid on-surface synthesis of different peptides. Combining this technique with click chemistry, we produced neo-glycopeptides directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well-defined glycan structures for multivalent display. We probed the two lectins concanavalin A and langerin with different glycans on multivalent scaffolds, revealing strong spacing-, density-, and ligand-dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding

Impact of glycan nature on structure and viscoelastic properties of glycopeptide hydrogels

Mucus is a complex biological hydrogel that acts as a barrier for almost everything entering or exiting the body. It is therefore of emerging interest for biomedical and pharmaceutical applications. Besides water, the most abundant components are the large and densely glycosylated mucins, glycoproteins of up to 20 MDa and carbohydrate content of up to 80 wt%. Here, we designed and explored a library of glycosylated peptides to deconstruct the complexity of mucus. Using the well-characterized hFF03 coiled-coil system as a hydrogel-forming peptide scaffold, we systematically probed the contribution of single glycans to the secondary structure as well as the formation and viscoelastic properties of the resulting hydrogels. We show that glycan-decoration does not affect α-helix and coiled-coil formation while it alters gel stiffness. By using oscillatory macrorheology, dynamic light scattering microrheology, and fluorescence lifetime-based nanorheology, we characterized the glycopeptide materials over several length scales. Molecular simulations revealed that the glycosylated linker may extend into the solvent, but more frequently interacts with the peptide, thereby likely modifying the stability of the self-assembled fibers. This systematic study highlights the interplay between glycan structure and hydrogel properties and may guide the development of synthetic mucus mimetics

Growth and poverty revisited from a multidimensional perspective

The actual impact of economic growth on poverty reduction is of fundamental importance to the development agenda. This paper offers new empirical evidence on growth and poverty measured from a multidimensional perspective using the global Multidimensional Poverty Index. Results from a First Difference Estimator Model suggest that while economic growth reduces multidimensional poverty, this impact is well below a one-to-one relationship and lower than the impact of growth on income poverty. Results from a cross-section model additionally suggest that countries with higher levels of exports, higher share of industry and services and higher control of corruption have lower multidimensional poverty

Growth and poverty revisited from a multidimensional perspective

The actual impact of economic growth on poverty reduction is of fundamental importance to the development agenda, especially in view of the Sustainable Development Goals. So far, studies have focused on income poverty. This paper offers new empirical evidence on growth and poverty measured from a multidimensional perspective using the global Multidimensional Poverty Index. Results from a first difference estimator model suggest that while economic growth reduces multidimensional poverty, this impact is well below a one-to-one relationship. We also find that economic growth has a far bigger impact on reducing income poverty than on reducing multidimensional poverty. Results from an alternative cross-section model also support this result and additionally suggest that countries with higher levels of exports, a higher share of industry and services in their GDPs, and higher control of corruption have lower multidimensional poverty. All in all, the results highlight the need for countries to grow in order to reduce poverty, but they simultaneously suggest the limited power of economic growth per se to achieve grand reductions in poverty

Growth and poverty revisited from a multidimensional perspective

The actual impact of economic growth on poverty reduction is of fundamental importance to the development agenda. This paper offers new empirical evidence on growth and poverty measured from a multidimensional perspective using the global Multidimensional Poverty Index. Results from a First Difference Estimator Model suggest that while economic growth reduces multidimensional poverty, this impact is well below a one-to-one relationship and lower than the impact of growth on income poverty. Results from a cross-section model additionally suggest that countries with higher levels of exports, higher share of industry and services and higher control of corruption have lower multidimensional poverty

NIZATIDINE 150 MG AT NIGHT IN THE PROPHYLAXIS OF GASTRIC-ULCER RELAPSE - A 12-MONTH PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND MULTICENTER STUDY VERSUS PLACEBO

bstract: Objective: To evaluate the safety and efficacy of nizatidine 150 mg as a maintenance therapy for gastric ulcer. Design: A 1-year prospective, multicentre, randomized, double-blind study versus placebo. All patients were examined every 3 months with endoscopy, clinical check-ups and blood tests. Setting: Outpatients followed-up by 22 endoscopic units in north-eastern Italy. Patients: Adult patients with an endoscopically documented healed gastric ulcer, obtained within 8 weeks by nizatidine 300 mg. Two hundred and forty-one patients entered the study: 123 treated with nizatidine 150 mg, 118 with placebo; one was excluded. Thirty-eight patients withdrew during follow-up, 202 concluded the study. Main outcome measures: Age, gender, height, weight, family history of ulcer disease, smoking habit, alcohol consumption, length of gastric ulcer history, previous ulcer treatment, number of ulcers, ulcer size and location, current drug therapy and common laboratory tests were taken into account. Results: Nizatidine proved significantly better than placebo in preventing gastric ulcer relapse, i.e. remission rate was 94 versus 79%, 81 versus 68%, 79 versus 640/o and 77 versus 52% after 3, 6, 9 and 12 months, respectively (P = 0.001). Antacid consumption, symptoms, compliance and adverse events were comparable in both groups; cigarette smoking was the major relapse risk factor in both treatment groups. Conclusion: Long-term nizatidine 150 mg per day proved safe and effective in containing gastric ulcer relapse compared with placebo: smoking habit is the most important risk factor in gastric ulcer relapse

Elastic behaviour and structural evolution of nanocrystalline Fe73.5Cu1Nb3Si13.5B9 produced by thermal ageing or joule-heating

Internal friction and dynamic Young's modulus versus temperature were measured in Fe73.5Cu1Nb3Si13.5B9 melt-spun ribbons as-prepared or after being submitted to Joule-heating treatments or to furnace annealing during isothermal modulus measurements. In Joule-heated samples the resistance was measured continuously during the heating treatments. Changes in the resistivity reflecting changes in the microstructure were correlated with room-temperature measurements of the magnetic permeability and the Delta E effect. The experimental results are discussed with specific reference to the microstructural evolution of the annealed ribbons from the initial amorphous phase to the nanocrystalline phase. A strong enhancement of the Delta E effect was found in Joule-heated ribbons just before the nanocrystalline phase formed