Generalised Osteoarthritis: from Mendelian Disorder to Complex Disease

Osteoarthritis (OA) is a prevalent and complex disorder with a high hereditary probability. Previous genetic research into OA has yielded several common gene variants contributing to joint specific OA phenotypes. Only a few studies allowed an examination of multiple joint sites in the patients included. In this thesis, we have focused, on the identification and investigation of OA susceptibility of rare and common generalised OA (GOA) in family based studies and common OA in the population. We investigated previously reported relationships between two candidate genes (FRZB and MATN3) with OA in a random sample from the population-based Rotterdam study and in siblings from the Genetics Osteoarthritis and Progression (GARP) study. A functional variant in FRZB indeed associates to OA but this seems not confined to hip only. Associations of MATN3 variants suggest that genetic variation in this gene determines susceptibility to spinal disc degeneration and OA of the first carpometacarpal joint. Different linkage areas were identified for early and late onset GOA. We mapped a major locus for OA at multiple joint sites on 14q32.11 in middle aged siblings from the GARP study and on 2q33.3 in seven early onset families. From our studies so far, DIO2, IDH1 and NRP2 may be new OA loci.LEI Universiteit LeidenNetherlands Organisation for Scientific Research (grant 904-61-095)Moleculair Epidemiologisch Onderzoek naar Complexe Ziekte

High microsatellite and SNP genotyping success rate established in a large number of genomic DNA samples extracted from mouth swabs and genotypes

In this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1-42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%-10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a genotyping success rate lower than 75% (range 58%-71 %) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs

Chiral radiative corrections and D_s(2317)/D(2308) mass puzzle

We show that one loop chiral corrections for heavy-light mesons in potential model can explain the small mass of D_s(2317) as well as the small mass gap between D_s(2317) and D(2308).Comment: To appear in EPJC. A figure and references addede

Current reversal with type-I intermittency in deterministic inertia ratchets

The intermittency is investigated when the current reversal occurs in a deterministic inertia ratchet system. To determine which type the intermittency belongs to, we obtain the return map of velocities of particle using stroboscopic recording, and numerically calculate the distribution of average laminar length ${}$. The distribution follows the scaling law of ${} \propto {\epsilon}^{-1/2}$, the characteristic relation of type-I intermittency.Comment: 4 pages, 7 figure

Gross tumour volume delineation in anal cancer on T2-weighted and diffusion-weighted MRI - Reproducibility between radiologists and radiation oncologists and impact of reader experience level and DWI image quality

Abstract Purpose To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality. Methods and materials We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients. Four readers (Senior and Junior Radiologist; Senior and Junior Radiation Oncologist) independently delineated GTVs, first on T2W-MRI only and then on DWI (with reference to T2W-MRI). Maximum Tumour Diameter (MTD) was calculated from each GTV. Mean GTVs/MTDs were compared between readers and between T2W-MRI vs. DWI. Interobserver agreement was calculated as Intraclass Correlation Coefficient (ICC), Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). DWI image quality was assessed using a 5-point artefact scale. Results Interobserver agreement between radiologists vs. radiation oncologists and between junior vs. senior readers was good–excellent, with similar agreement for T2W-MRI and DWI (e.g. ICCs 0.72–0.94 for T2W-MRI and 0.68–0.89 for DWI). There was a trend towards smaller GTVs on DWI, but only for the radiologists (P = 0.03–0.07). Moderate-severe DWI-artefacts were observed in 11/25 (44%) cases. Agreement tended to be lower in these cases. Conclusion Overall interobserver agreement for anal cancer GTV delineation on MRI is good for both radiologists and radiation oncologists, regardless of experience level. Use of DWI did not improve agreement. DWI artefacts affecting GTV delineation occurred in almost half of the patients, which may severely limit the use of DWI for radiotherapy planning if no steps are undertaken to avoid them

A Systematic Study on Energy Dependence of Quasi-Periodic Oscillation Frequency in GRS 1915+105

Systematically studying all the RXTE/PCA observations for GRS 1915+105 before November 2010, we have discovered three additional patterns in the relation between Quasi-Periodic Oscillation (QPO) frequency and photon energy, extending earlier outcomes reported by Qu et al. (2010). We have confirmed that as QPO frequency increases, the relation evolves from the negative correlation to positive one. The newly discovered patterns provide new constraints on the QPO models

CP violation in chargino decays in the MSSM

In the minimal supersymmetric standard model (MSSM) with complex parameters, supersymmetric loop effects can lead to \emph{CP} violation. We calculate the rate asymmetries of decays of charginos into the lightest neutralino and a $W$ boson on the basis of the most important loop contributions in the third generation squark sectors. It turns out that the \emph{CP} violating asymmetries can be a few per cent in typical regions of the parameter space of the MSSM. These processes would provide very promising channels for probing \emph{CP} violation in the MSSM at future high-energy colliders.Comment: 15 pages, 5 figures, LaTeX2

Metropolis simulations of Met-Enkephalin with solvent-accessible area parameterizations

We investigate the solvent-accessible area method by means of Metropolis simulations of the brain peptide Met-Enkephalin at 300$K$. For the energy function ECEPP/2 nine atomic solvation parameter (ASP) sets are studied. The simulations are compared with one another, with simulations with a distance dependent electrostatic permittivity $\epsilon (r)$, and with vacuum simulations ($\epsilon =2$). Parallel tempering and the biased Metropolis techniques RM$_1$ are employed and their performance is evaluated. The measured observables include energy and dihedral probability densities (pds), integrated autocorrelation times, and acceptance rates. Two of the ASP sets turn out to be unsuitable for these simulations. For all other systems selected configurations are minimized in search of the global energy minima, which are found for the vacuum and the $\epsilon(r)$ system, but for none of the ASP models. Other observables show a remarkable dependence on the ASPs. In particular, we find three ASP sets for which the autocorrelations at 300$$K are considerably smaller than for vacuum simulations.Comment: 10 pages and 8 figure

Probing Topcolor-Assisted Technicolor from Top-Charm Associated Production at LHC

We propose to probe the topcolor-assisted technicolor (TC2) model from the top-charm associated productions at the LHC, which are highly suppressed in the Standard Model. Due to the flavor-changing couplings of the top quark with the scalars (top-pions and top-Higgs) in TC2 model, the top-charm associated productions can occur via both the s-channel and t-channel parton processes by exchanging a scalar field at the LHC. We examined these processes through Monte Carlo simulation and found that they can reach the observable level at the LHC in quite a large part of the parameter space of the TC2 model.Comment: Version to appear in PRD (Rapid Communication

Virtual Effects of Split SUSY in Higgs Productions at Linear Colliders

In split supersymmetry the gauginos and higgsinos are the only supersymmetric particles possibly accessible at foreseeable colliders like the CERN Large Hadron Collider (LHC) and the International Linear Collider (ILC). In order to account for the cosmic dark matter measured by WMAP, these gauginos and higgsinos are stringently constrained and could be explored at the colliders through their direct productions and/or virtual effects in some processes. The clean environment and high luminosity of the ILC render the virtual effects of percent level meaningful in unraveling the new physics effects. In this work we assume split supersymmetry and calculate the virtual effects of the WMAP-allowed gauginos and higgsinos in Higgs productions e+e- -> Z h and e+e- -> \nu_e \bar_\nu_e h through WW fusion at the ILC. We find that the production cross section of e+e- -> Zh can be altered by a few percent in some part of the WMAP-allowed parameter space, while the correction to the WW-fusion process e+e- -> \nu_e \bar_\nu_e h is below 1%. Such virtual effects are correlated with the cross sections of chargino pair productions and can offer complementary information in probing split supersymmetry at the colliders.Comment: more discussions added (7 pages, 10 figs