Local structure of percolating gels at very low volume fractions

The formation of colloidal gels is strongly dependent on the volume fraction of the system and the strength of the interactions between the colloids. Here we explore very dilute solutions by the means of numerical simulations, and show that, in the absence of hydrodynamic interactions and for sufficiently strong interactions, percolating colloidal gels can be realised at very low values of the volume fraction. Characterising the structure of the network of the arrested material we find that, when reducing the volume fraction, the gels are dominated by low-energy local structures, analogous to the isolated clusters of the interaction potential. Changing the strength of the interaction allows us to tune the compactness of the gel as characterised by the fractal dimension, with low interaction strength favouring more chain-like structures

Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling

Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the cholesterol moiety covalently linked to HH ligands, thereby preventing this SHH-attached cholesterol from binding to the HH receptor Patched (PTCH1). We also present the structure of the HHIP C-terminal domain in complex with the GAG heparin. Heparin can bind to both HHIP-N and HHIP-C, thereby inducing clustering at the cell surface and generating a high-avidity platform for SHH sequestration and inhibition. Our data suggest a multimodal mechanism, in which HHIP can bind two specific sites on the SHH morphogen, alongside multiple GAG interactions, to inhibit SHH signalling

The quantum mechanical geometric phase of a particle in a resonant vibrating cavity

We study the general-setting quantum geometric phase acquired by a particle in a vibrating cavity. Solving the two-level theory with the rotating-wave approximation and the SU(2) method, we obtain analytic formulae that give excellent descriptions of the geometric phase, energy, and wavefunction of the resonating system. In particular, we observe a sudden $\pi$-jump in the geometric phase when the system is in resonance. We found similar behaviors in the geometric phase of a spin-1/2 particle in a rotating magnetic field, for which we developed a geometrical model to help visualize its evolution.Comment: 15pages,6figure

On convergent series representations of Mellin-Barnes integrals

Multiple Mellin-Barnes integrals are often used for perturbative calculations in particle physics. In this context, the evaluation of such objects may be performed through residues calculations which lead to their expression as multiple series in powers and logarithms of the parameters involved in the problem under consideration. However, in most of the cases, several series representations exist for a given integral. They converge in different regions of values of the parameters, and it is not obvious to obtain them. For twofold integrals we present a method which allows to derive straightforwardly and systematically: (a) different sets of poles which correspond to different convergent double series representations of a given integral, (b) the regions of convergence of all these series (without an a priori full knowledge of their general term), and (c) the general term of each series (this may be performed, if necessary, once the relevant domain of convergence has been found). This systematic procedure is illustrated with some integrals which appear, among others, in the calculation of the two-loop hexagon Wilson loop in N = 4 SYM theory. Mellin-Barnes integrals of higher dimension are also considered.Comment: 49 pages, 16 figure

Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys

Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic

Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease

Chronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 × 10-7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 × 10-9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus

Patient presentation and physician management of upper respiratory tract infections: A retrospective review of over 5 million primary clinic consultations in Hong Kong

Background: Upper respiratory tract infection (URTI) has a significant healthcare burden worldwide. Considerable resources are consumed through health care consultations and prescribed treatment, despite evidence for little or no effect on recovery. Patterns of consultations and care including use of symptomatic medications and antibiotics for upper respiratory tract infections are poorly described. Methods. We performed a retrospective review of computerized clinical data on patients presenting to all public primary care clinics in Hong Kong with symptoms of respiratory tract infections. International Classification of Primary care (ICPC)codes used to identify patients included otitis media (H71), streptococcal pharyngitis (R72), acute URTI (R74), acute sinusitis (R75), acute tonsillitis (R76), acute laryngitis (R77), and influenza (R80). Sociodemographic variables such as gender, age, chronic illness status, attendance date, type and duration of drug prescribed were also collected. Results: Of the 5,529,755 primary care consultations for respiratory symptoms from 2005 to 2010, 98% resulted in a prescription. Prescription patterns of symptomatic medication were largely similar across the 5 years. In 2010 the mean number of drugs prescribed per consultation was 3.2, of which the commonly prescribed medication were sedating antihistamines (79.9%), analgesia (58.9%), throat lozenges (40.4%) and expectorant cough syrup (33.8%). During the study period, there was an overall decline in antibiotic prescription (8.1% to 5.1%). However, in consultations where the given diagnosis was otitis media (H71), streptococcal pharyngitis (R72), acute sinusitis (R75) or acute laryngitis (R76), over 90% resulted in antibiotic prescription. Conclusion: There was a decline in overall antibiotic prescription over the study period. However, the use of antibiotics was high in some conditions e.g. otitis media and acute laryngitis a. Multiple symptomatic medications were given for upper respiratory tract infections. Further research is needed to develop clinical and patients directed interventions to reduce the number of prescriptions of symptomatic medications and antibiotics that could reduce costs for health care services and iatrogenic risk to patients. © 2014 Kung et al.; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Effective and Asymptotic Critical Exponents of Weakly Diluted Quenched Ising Model: 3d Approach Versus ϵ1/2\epsilon^{1/2}-Expansion

We present a field-theoretical treatment of the critical behavior of three-dimensional weakly diluted quenched Ising model. To this end we analyse in a replica limit n=0 5-loop renormalization group functions of the $\phi^4$-theory with O(n)-symmetric and cubic interactions (H.Kleinert and V.Schulte-Frohlinde, Phys.Lett. B342, 284 (1995)). The minimal subtraction scheme allows to develop either the $\epsilon^{1/2}$-expansion series or to proceed in the 3d approach, performing expansions in terms of renormalized couplings. Doing so, we compare both perturbation approaches and discuss their convergence and possible Borel summability. To study the crossover effect we calculate the effective critical exponents providing a local measure for the degree of singularity of different physical quantities in the critical region. We report resummed numerical values for the effective and asymptotic critical exponents. Obtained within the 3d approach results agree pretty well with recent Monte Carlo simulations. $\epsilon^{1/2}$-expansion does not allow reliable estimates for d=3.Comment: 35 pages, Latex, 9 eps-figures included. The reference list is refreshed and typos are corrected in the 2nd versio

The human gut symbiont <i>Ruminococcus gnavus</i> shows specificity to blood group A antigen during mucin glycan foraging:Implication for niche colonisation in the gastrointestinal tract

The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-β-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection

The human gut symbiont <i>Ruminococcus gnavus</i> shows specificity to blood group A antigen during mucin glycan foraging:Implication for niche colonisation in the gastrointestinal tract

The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-β-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection