Search results

Filter

Filetype

Your search for "*" yielded 538321 hits

Global Legitimacy Crises : Decline and Revival in Multilateral Governance

Presents new conceptualization of legitimacy crises in global governanceOffers new theoretical ideas on legitimacy crises as activation that can yield positive as well as negative consequencesProvides a comparative assessment of legitimacy crises and their consequences in 32 international organizations and across three decadesDevelops in-depth insights on the legitimacy crises of the WTO and the U

Generation of two compound heterozygous HGSNAT-mutated lines from healthy induced pluripotent stem cells using CRISPR/Cas9 to model Sanfilippo C syndrome

Sanfilippo C syndrome (Mucopolysaccharidosis IIIC) is a rare lysosomal storage disorder caused by mutations in the HGSNAT gene. It is characterized by a progressive and severe neurodegeneration, for which there is no treatment available. Here, we report the generation of two HGSNAT-mutated cell lines from a healthy human induced pluripotent stem cell (hiPSC) line using CRISPR/Cas9 editing. These n

Transcription Factor-Forced Astrocytic Differentiation Impairs Human Glioblastoma Growth In Vitro and In Vivo

Direct cellular reprogramming has recently gained attention of cancer researchers for the possibility to convert undifferentiated cancer cells into more differentiated, postmitotic cell types. While a few studies have attempted reprogramming of glioblastoma (GBM) cells toward a neuronal fate, this approach has not yet been used to induce differentiation into other lineages and in vivo data on redu

Spectroscopy along flerovium decay chains. II. Fine structure in odd-A 289Fl

Fifteen correlated α-decay chains starting from the odd-A superheavy nucleus 289Fl were observed following the fusion-evaporation reaction 48Ca+244Pu. The results call for at least two parallel α-decay sequences starting from at least two different states of 289Fl. This implies that close-lying levels in nuclei along these chains have quite different spin-parity assignments. Further, observed α-el

Spectroscopy along flerovium decay chains. III. Details on experiment, analysis, 282Cn, and spontaneous fission branches

Flerovium isotopes (element Z = 114) were produced in the fusion-evaporation reactions 48Ca+242,244Pu and studied with an upgraded TASISpec decay station placed in the focal plane of the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Twenty-nine flerovium decay chains were identified by means of correlated implantation, α decay, and spontaneo

SPACAP Working Paper No. 1 : How do Swedish Public Agencies understand, approach and operationalize Capacity Development work abroad?

Capacity development (CapDev) support through various Swedish public agencies (SPA) to their sister authorities in low- and middle-income countries has been a salient feature of Sweden’s institutional development cooperation since the1980s. Despite constituting a small percentage of Swedish aid, the scale and scope of SPAs engagement in CapDev work abroad deserves more attention than currently bei

SPACAP Working Paper No. 2 : How do Swedish Public Agencies understand, approach and operationalize Capacity Development work abroad?

This summary addresses the overall results of the Swedish Public Agencies’ Capacity Development (SPACAP) study that started in December 2018, whereas the main body of this second, and final, Working Paper mainly focusses on the way forward. SPACAP is a Sida funded one-year study project conducted byLund University in collaboration with the SPAs’ Network for Learning (N4L), which aims at providing

Galectin-8 Downmodulates TLR4 Activation and Impairs Bacterial Clearance in a Mouse Model of Pseudomonas aeruginosa Keratitis

Pseudomonas aeruginosa provokes a painful, sight-threatening corneal infection. It progresses rapidly and is difficult to treat. In this study, using a mouse model of P. aeruginosa keratitis, we demonstrate the importance of a carbohydrate-binding protein, galectin-8 (Gal-8), in regulation of the innate immune response. First, using two distinct strains of P. aeruginosa, we established that Gal-8−

The role of Galectin-3 in α-synuclein-induced microglial activation

Background: Parkinson's disease (PD) is the most prevalent neurodegenerative motor disorder. The neuropathology is characterized by intraneuronal protein aggregates of α-synuclein and progressive degeneration of dopaminergic neurons within the substantia nigra. Previous studies have shown that extracellular α-synuclein aggregates can activate microglial cells, induce inflammation and contribute to

Ligand binding and complex formation of galectin-3 is modulated by pH variations

Galectin-3-dependent clusters or lattices are formed at the surface as well as in distinct organelles of eukaryotic cells. Incorporation into membrane proximal networks can fix glycoproteins within subcellular domains or sort them into distinct transport pathways. In the present paper we analysed the effect of acidification on the sugar binding and self-oligomerization of galectin-3. Using a fluor

Bacterial adhesion of Streptococcus suis to host cells and its inhibition by carbohydrate ligands

Streptococcus suis is a Gram-positive bacterium, which causes sepsis and meningitis in pigs and humans. This review examines the role of known S. suis virulence factors in adhesion and S. suis carbohydrate-based adhesion mechanisms, as well as the inhibition of S. suis adhesion by anti-adhesion compounds in in vitro assays. Carbohydrate-binding specificities of S. suis have been identified, and th

A study of the donor properties of sialyl phosphites having an auxiliary 3-(S)-phenylseleno group

Two phosphite sialyl donors, each having an auxiliary 3-(S)-phenylseleno group, were prepared and evaluated. The phenylseleno group was introduced via a new mode of generating phenylselenenic acid (‘PhSeOH’). Although the sialyl donors provided fair yields (32–76%) of the desired sialosides in glycosylations of the reactive acceptor 1,2;3,4-di-O-isopropylidene-α-d-galactopyranose, no sialylated pr

An efficient and convergent route towards water-soluble, chiral and amphiphilic macrocycles

A practical procedure for the synthesis of water-soluble, chiral and amphiphilic macrocyclic molecules is described. Acylation of p-xylylene diamine with Fmoc-protected glycine and aspartic acid, followed by removal of the Fmoc moiety afforded amino acid:p-xylene conjugates as free diamines. These diamines were converted to symmetrical and unsymmetrical macrocycles via stepwise urea formation u

The p-methoxybenzyl ether as an in situ-removable carbohydrate-protecting group : A simple one-pot synthesis of the globotetraose tetrasaccharide

A one-pot synthesis of the globotetraose tetrasaccharide is reported. The synthetic method relies on the use of a p-methoxybenzyl ether as an in situ-removable protecting group. N-Iodosuccinimide/trifluoromethanesulfonic acid-promoted glycosylation of 2-bromoethyl-2,3,6-tri-O-benzoyl-4-O-(2,3,6-tri-O-benzoyl-β-D-galactopyranosyl)-β-D-glucopyranoside 5 at −45 °C with phenyl 2,4,6-tri-O-benzyl-3-O-(

Solid-phase extraction for combinatorial libraries

Solid-phase extraction (SPE) has during the last three years emerged as a convenient method for the purification of compound libraries prepared by solution synthesis. The widespread use of SPE in combinatorial chemistry can be explained by straightforward SPE method development facilitated by the availability of numerous commercial SPE resins. High-speed automated SPE is readily accomplished by ta

Conversion of 2-(trimethylsilyl)ethyl sulfides into thioesters

Treatment of 2-(trimethylsilyl)ethyl sulfides with a carboxylic acid chloride and AgBF4 in CH2Cl2 furnishes the corresponding thioesters in high yields and purities. The conversion of 2-(trimethylsilyl)ethyl sulfides into synthetically versatile thioesters allows such sulfides to be used as sulfhydryl protective groups, since such sulfides are easily prepared and are stable towards many reaction c

Parallel solution synthesis of a 'carbohybrid' library designed to inhibit galactose-binding proteins

Parallel solution S-alkylations of a 1-thio-β-D-galactopyranoside derivative with Michael acceptors and α-chloroketones, followed by ketone reductions, reductive aminations, and acylations were developed to yield a library of 1-thio-β-D-galactopyranosides carrying small and diverse polar- neutral, hydrophobic, aromatic, cationic, or anionic non-carbohydrate aglycon structures. Screening of the lib

Comparative 1H NMR study of hydroxy protons in galabioside and its S-linked 4-thiodisaccharide analogue in aqueous solution

The NMR data obtained from hydroxy protons have been used to investigate the presence and absence of intramolecular hydrogen bonding in aqueous solutions of 2-(trimethylsilyl)ethyl galabioside (α-D-Galp-(1→4)-β-D-Galp-O(CH2)2SiMe3) and the S-linked 4-thiodisaccharide analogue. The data show that there is a weak hydrogen bond interaction between O-6H and O-2'H in galabioside, but not in the thio-an

Solid-phase extraction on C18 silica as a purification strategy in the solution synthesis of a 1-Thio-β-D-galactopyranoside library

A novel strategy for the purification of carbohydrate-based chemical libraries synthesized in solution was developed. Purification of reaction products was accomplished by means of solid-phase extraction enabled by protecting the 2-, 3-, 4-, and 6-hydroxyl groups of a galactose derivative as their hydrophobic O-laurates. The presence of multiple O-laurates allowed adsorption of reaction products o

Immobilization of reducing sugars as toxin binding agents

A simple and economical procedure for the attachment of reducing sugars to aminated solid supports has been developed. Reaction of the amino groups on the solid support with p-nitrophenyl chloroformate, followed by 1,6-hexanediamine, yields a chain-extended amine to which reducing sugars can be attached while remaining accessible to macromolecules. Immobilization of the reducing sugars involves a