Glycosylated nanoparticles as efficient antimicrobial delivery agents

Synthetic polymer nanoparticles that can be tailored through multivalent ligand display on the surface, while at the same time allowing encapsulation of desired bioactive molecules, are especially useful in providing a versatile and robust platform in the design of specific delivery vehicles for various purposes. Glycosylated nanoparticles (glyco-NPs) of a poly(n-butyl acrylate) (pBA) core and poly(N-2-(β-d-glucosyloxy)ethyl acrylamide) (p(NβGlcEAM)) or poly(N-2-(β-D-galactosyloxy)ethyl acrylamide) (p(NβGalEAM)) corona were prepared via nanoprecipitation in aqueous solutions of preformed amphiphilic glycopolymers. Well-defined block copolymers of (poly(pentafluorophenyl acrylate) (pPFPA) and pBA were first prepared by RAFT polymerization followed by postpolymerization functionalization with aminoethyl glycosides to yield p(NβGlcEAM-b-BA) and p(NβGalEAM-b-BA), which were then used to form glyco-NPs (glucosylated and galactosylated NPs, Glc-NPs and Gal-NPs, respectively). The glyco-NPs were characterized by dynamic light scattering (DLS) and TEM. Encapsulation and release of ampicillin, leading to nanoparticles that we have termed “glyconanobiotics”, were studied. The ampicillin-loaded glyco-NPs were found to induce aggregation of Staphylococcus aureus and Escherichia coli and resulted in antibacterial activity approaching that of ampicillin itself. This glyconanobiotics strategy represents a potential new approach for the delivery of antibiotics close to the surface of bacteria by promoting bacterial aggregation. Defined release in the proximity of the bacterial envelope may thus enhance antibacterial efficiency and potentially reduce the quantities of agent required for potency

Galactose-Functionalized PolyHIPE Scaffolds for Use in Routine Three Dimensional Culture of Mammalian Hepatocytes

Three-dimensional (3D) cell culture is regarded as a more physiologically relevant method of growing cells in the laboratory compared to traditional monolayer cultures. Recently, the application of polystyrene-based scaffolds produced using polyHIPE technology (porous polymers derived from high internal phase emulsions) for routine 3D cell culture applications has generated very promising results in terms of improved replication of native cellular function in the laboratory. These materials, which are now available as commercial scaffolds, are superior to many other 3D cell substrates due to their high porosity, controllable morphology, and suitable mechanical strength. However, until now there have been no reports describing the surface-modification of these materials for enhanced cell adhesion and function. This study, therefore, describes the surface functionalization of these materials with galactose, a carbohydrate known to specifically bind to hepatocytes via the asialoglycoprotein receptor (ASGPR), to further improve hepatocyte adhesion and function when growing on the scaffold. We first modify a typical polystyrene-based polyHIPE to produce a cell culture scaffold carrying pendent activated-ester functionality. This was achieved via the incorporation of pentafluorophenyl acrylate (PFPA) into the initial styrene (STY) emulsion, which upon polymerization formed a polyHIPE with a porosity of 92% and an average void diameter of 33 μm. Histological analysis showed that this polyHIPE was a suitable 3D scaffold for hepatocyte cell culture. Galactose-functionalized scaffolds were then prepared by attaching 2′-aminoethyl-β-D-galactopyranoside to this PFPA functionalized polyHIPE via displacement of the labile pentafluorophenyl group, to yield scaffolds with approximately ca. 7−9% surface carbohydrate. Experiments with primary rat hepatocytes showed that cellular albumin synthesis was greatly enhanced during the initial adhesion/settlement period of cells on the galactose-functionalized material, suggesting that the surface carbohydrates are accessible and selective to cells entering the scaffold. This porous polymer scaffold could, therefore, have important application as a 3D scaffold that offers enhanced hepatocyte adhesion and functionality

Constructing and Characterising Solar Structure Models for Computational Helioseismology

In this paper, we construct background solar models that are stable against convection, by modifying the vertical pressure gradient of Model S (Christensen-Dalsgaard et al., 1996, Science, 272, 1286) relinquishing hydrostatic equilibrium. However, the stabilisation affects the eigenmodes that we wish to remain as close to Model S as possible. In a bid to recover the Model S eigenmodes, we choose to make additional corrections to the sound speed of Model S before stabilisation. No stabilised model can be perfectly solar-like, so we present three stabilised models with slightly different eigenmodes. The models are appropriate to study the f and p1 to p4 modes with spherical harmonic degrees in the range from 400 to 900. Background model CSM has a modified pressure gradient for stabilisation and has eigenfrequencies within 2% of Model S. Model CSM_A has an additional 10% increase in sound speed in the top 1 Mm resulting in eigenfrequencies within 2% of Model S and eigenfunctions that are, in comparison with CSM, closest to those of Model S. Model CSM_B has a 3% decrease in sound speed in the top 5 Mm resulting in eigenfrequencies within 1% of Model S and eigenfunctions that are only marginally adversely affected. These models are useful to study the interaction of solar waves with embedded three-dimensional heterogeneities, such as convective flows and model sunspots. We have also calculated the response of the stabilised models to excitation by random near-surface sources, using simulations of the propagation of linear waves. We find that the simulated power spectra of wave motion are in good agreement with an observed SOHO/MDI power spectrum. Overall, our convectively stabilised background models provide a good basis for quantitative numerical local helioseismology. The models are available for download from http://www.mps.mpg.de/projects/seismo/NA4/.Comment: 35 pages, 23 figures Changed title Updated Figure 1

On hyperovals of polar spaces

We derive lower and upper bounds for the size of a hyperoval of a finite polar space of rank 3. We give a computer-free proof for the uniqueness, up to isomorphism, of the hyperoval of size 126 of H(5, 4) and prove that the near hexagon E-3 has up to isomorphism a unique full embedding into the dual polar space DH(5, 4)

Involvement of metabolic and immune responses in the pathogenesis of Abacavir hypersensitivity reaction

Oral presentatio

A range of catalytic efficiencies with avian retroviral protease subunits genetically linked to form single polypeptide chains

Molecular modeling based on the crystal structure of the Rous sarcoma virus (RSV) protease dimer has been used to link the two identical subunits of this enzyme into a functional, single polypeptide chain resembling the nonviral aspartic proteases. Six different linkages were selected to test the importance of different interactions between the amino acids at the amino and carboxyl termini of the two subunits. These linkages were introduced into molecular clones of fused protease genes and the linked protease dimers were expressed in Escherichia coli and purified. Catalytically active proteins were obtained from the inclusion body fraction after renaturation. The linked protease dimers exhibited a 10-20-fold range in catalytic efficiencies (V(max)/K(m)) on peptide substrates. Both flexibility and ionic interactions in the linkage region affect catalytic efficiency. Some of the linked protease dimers were 2-3-fold more active than the nonlinked enzyme purified from bacteria, although substrate specificities were unchanged. Similar relative efficiencies were observed using a polyprotein precursor as substrate. Mutation of one catalytic Asp in the most active linked protease dimer inactivated the enzyme, demonstrating that these proteins function as single polypeptide chains rather than as multimers

A method for isolating and culturing placental cells from failed early equine pregnancies

Early pregnancy loss occurs in 6–10% of equine pregnancies making it the main cause of reproductive wastage. Despite this, reasons for the losses are known in only 16% of cases. Lack of viable conceptus material has inhibited investigations of many potential genetic and pathological causes. We present a method for isolating and culturing placental cells from failed early equine pregnancies. Trophoblast cells from 18/30 (60%) failed equine pregnancies of gestational ages 14–65 days were successfully cultured in three different media, with the greatest growth achieved for cells cultured in AmnioChrome™ Plus. Genomic DNA of a suitable quality for molecular assays was also isolated from 29/30 of these cases. This method will enable future investigations determining pathologies causing EPL

The future of work in shaping the employment inclusion of young adults with disabilities:a qualitative study

Purpose: The world of work is changing and creating challenges and opportunities for the employment inclusion of young people with disabilities. In this article, the perceptions held by young adults with disabilities regarding participation in the future of work are examined. Design/methodology/approach: One-on-one interviews were conducted with Canadian young adults (ages 18–36 years) living with a disability. Participants were asked about their thoughts regarding the impact of the changing nature of work on their labor market involvement and career aspirations. A thematic analysis was performed to identify and examine emergent salient themes. Findings: In total, 22 young adults were interviewed; over half held secure employment. Career aspirations and work-related decisions were primarily shaped by a participant's health needs. The future of work was seen as a more proximal determinant to employment. Digital technologies were expected to impact working conditions and create barriers and facilitators to employment. Participants who indicated being securely employed held positive expectations regarding the impact of digital technology on their work. Participants working precariously held negative appraisals regarding the impact of digital technologies on employment opportunities. The role of technological and soft skills was critical to participating in a labor market reliant on advanced technology. Participants reported barriers to developing job skills related to their disability and their work arrangements. Originality/value: This research highlights the importance of considering changes in the future of work, especially the digital transformation of the economy, in the design of initiatives which promote the employment inclusion of young adults with disabilities. Despite the significance of the changing nature of work, supporting health needs and encouraging access to secure work arrangements also remain paramount.</p

Magnetar outbursts: an observational review

Transient outbursts from magnetars have shown to be a key property of their emission, and one of the main way to discover new sources of this class. From the discovery of the first transient event around 2003, we now count about a dozen of outbursts, which increased the number of these strongly magnetic neutron stars by a third in six years. Magnetar outbursts might involve their multi-band emission resulting in an increased activity from radio to hard X-ray, usually with a soft X-ray flux increasing by a factor of 10-1000 with respect to the quiescent level. A connected X-ray spectral evolution is also often observed, with a spectral softening during the outburst decay. The flux decay times vary a lot from source to source, ranging from a few weeks to several years, as also the decay law which can be exponential-like, a power-law or even multiple power-laws can be required to model the flux decrease. We review here on the latest observational results on the multi-band emission of magnetars, and summarize one by one all the transient events which could be studied to date from these sources.Comment: 34 pages, 6 figures. Chapter of the Springer Book ASSP 7395 "High-energy emission from pulsars and their systems", proceeding of the Sant Cugat Forum on Astrophysics (12-16 April 2010). Review updated to January 201

Spin observables in deuteron-proton radiative capture at intermediate energies

A radiative deuteron-proton capture experiment was carried out at KVI using polarized-deuteron beams at incident energies of 55, 66.5, and 90 MeV/nucleon. Vector and tensor-analyzing powers were obtained for a large angular range. The results are interpreted with the help of Faddeev calculations, which are based on modern two- and three-nucleon potentials. Our data are described well by the calculations, and disagree significantly with the observed tensor anomaly at RCNP.Comment: 10 pages, 4 figures, submitted to PL