Beam-Charge Asymmetry associated with DVCS at HERMES

We report the first observation of an azimuthal asymmetry in the hard electroproduction of real photons with respect to the charge of the incoming lepton beam. The asymmetry is attributed to the interference between the Bethe-Heitler process and the deeply-virtual Compton scattering process, which gives access to the latter at the amplitude level. This process appears to be the theoretically cleanest way to access generalized parton distributions. The data have been accumulated by the HERMES experiment at DESY, scattering the HERA 27.6 GeV electron/positron beam off an unpolarized hydrogen gas target.Comment: 4 pages, 2 figures. Contribution to the European Workshop on the QCD Structure of the Nucleon (QCD - N'02), Ferrara, Italy, 3-6 Apr 2002, to be published in Nucl. Phys.

Deeply-Virtual Compton Scattering on Deuterium and Neon at HERMES

We report the first observation of azimuthal beam-spin asymmetries in hard electroproduction of real photons off nuclei. Attributed to the interference between the Bethe-Heitler process and the deeply-virtual Compton scattering process, the asymmetry gives access to the latter at the amplitude level. This process appears to be the theoretically cleanest way to access generalized parton distributions. The data presented here have been accumulated by the HERMES experiment at DESY, scattering the HERA 27.6 GeV positron beam off deuterium and neon gas targets.Comment: 5 pages, 6 figures. Talk given by F. Ellinghaus at the "15th International Spin Physics Symposium", SPIN 2002, September 9-14, 2002, BNL, Upton, NY, USA. To be published in the proceeding

Compromised Bone Healing in Aged Rats Is Associated With Impaired M2 Macrophage Function

Fracture repair is initiated by a multitude of immune cells and induction of an inflammatory cascade. Alterations in the early healing response due to an aged adaptive immune system leads to impaired bone repair, delayed healing or even formation of non-union. However, immuno-senescence is not limited to the adaptive immunity, but is also described for macrophages, main effector cells from the innate immune system. Beside regulation of pro- and anti-inflammatory signaling, macrophages contribute to angiogenesis and granulation tissue maturation. Thus, it seems likely that an altered macrophage function due to aging may affect bone repair at various stages and contribute to age related deficiencies in bone regeneration. To prove this hypothesis, we analyzed the expression of macrophage markers and angiogenic factors in the early bone hematoma derived from young and aged osteotomized Spraque Dawley rats. We detected an overall reduced expression of the monocyte/pan-macrophage markers CD14 and CD68 in aged rats. Furthermore, the analysis revealed an impaired expression of anti-inflammatory M2 macrophage markers in hematoma from aged animals that was connected to a diminished revascularization of the bone callus. To verify that the age related disturbed bone regeneration was due to a compromised macrophage function, CD14+ macrophage precursors were transplanted locally into the osteotomy gap of aged rats. Transplantation rescued bone regeneration partially after 6 weeks, demonstrated by a significantly induced deposition of new bone tissue, reduced fibrosis and significantly improved callus vascularization

The target asymmetry in hard vector-meson electroproduction and parton angular momenta

The target asymmetry for electroproduction of vector mesons is investigated within the handbag approach. While the generalized parton distribution (GPD) H is taken from a previous analysis of the elctroproduction cross section, we here construct the GPD E from double distributions and constrain it by the Pauli form factors of the nucleon, positivity bounds and sum rules. Predictions for the target asymmetry are given for various vector mesons and discussed how experimental data on the asymmetry will further constrain E and what we may learn about the angular momenta the partons carry.Comment: 24 pages, 11 figures, late

Understanding the proton's spin structure

We discuss the tremendous progress that has been towards an understanding of how the spin of the proton is distributed on its quark and gluon constituents. This is a problem that began in earnest twenty years ago with the discovery of the proton ``spin crisis'' by the European Muon Collaboration. The discoveries prompted by that original work have given us unprecedented insight into the amount of spin carried by polarized gluons and the orbital angular momentum of the quarks.Comment: Review article for J. Phys. G, 1 figure, 22 page

Fine Mapping Major Histocompatibility Complex Associations in Psoriasis and Its Clinical Subtypes

Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C*06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 x 10(-364)). Stepwise analysis revealed multiple HLA-C*06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C*12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQ alpha 1 amino acid position 53; p \u3c 5.0 x 10(-8)), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (P-omnibus = 2.2 x 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC

Pion production in deeply virtual Compton scattering

Using a soft pion theorem based on chiral symmetry and a $\Delta(1232)$ resonance model we propose an estimate for the production cross section of low energy pions in the deeply virtual Compton scattering (DVCS) process. In particular, we express the $e p \to e \gamma \pi N$ processes in terms of generalized parton distributions. We provide estimates of the contamination of the $e p \to e \gamma p$ DVCS observables due to this associated pion production processes when the experimental data are not fully exclusive, for a set of kinematical conditions representative of present or planned experiments at JLab, HERMES and COMPASS.Comment: 50 pages, 22 figure

Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome

Multiple synostoses syndrome 2 (SYNS2) is a rare genetic disease characterized by multiple fusions of the joints of the extremities, like phalangeal joints, carpal and tarsal joints or the knee and elbows. SYNS2 is caused by point mutations in the Growth and Differentiation Factor 5 (GDF5), which plays an essential role during skeletal development and regeneration. We selected one of the SYNS2-causing GDF5 mutations, p.N445T, which is known to destabilize the interaction with the Bone Morphogenetic Protein (BMP) antagonist NOGGIN (NOG), in order to generate the superagonistic GDF5 variant GDF5(N445T). In this study, we tested its capacity to support regeneration in a rat critical-sized defect model in vivo. MicroCT and histological analyses indicate that GDF5(N445T)-treated defects show faster and more efficient healing compared to GDF5 wild type (GDF5(wt))-treated defects. Microarray-based gene expression and quantitative PCR analyses from callus tissue point to a specific acceleration of the early phases of bone healing, comprising the inflammation and chondrogenesis phase. These results support the concept that disease-deduced growth factor variants are promising lead structures for novel therapeutics with improved clinical activities

Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing

Bone formation as well as bone healing capacity is known to be impaired in the elderly. Although bone formation is outpaced by bone resorption in aged individuals, we hereby present a novel path that considerably impacts bone formation and architecture: Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. The role of the aging immune system on bone homeostasis and on the bone healing cascade has so far not been considered. Within this study mice at different age and immunological experience were analyzed toward bone properties. Healing was assessed by introducing an osteotomy, immune cells were adoptively transferred to disclose the difference in biological vs. chronological aging. In vitro studies were employed to test the interaction of immune cell products (cytokines) on cells of the musculoskeletal system. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Furthermore, bone formation is also impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. We show the impact of an experienced immune system compared to a naive immune system, demonstrating the substantial differences in the healing capacity and bone homeostasis due to the immune composition. We further showed that in vivo mechanical stimulation changed the immune system phenotype in young mice toward a more naive composition. While this rescue was found to be significant in young individuals, aged mice only showed a trend toward the reconstitution of a more naive immune phenotype. Considering the immune system's experience level in an individual, will likely allow one to differentiate (stratify) and treat (immune-modulate) patients more effectively. This work illustrates the relevance of including immune diagnostics when discussing immunomodulatory therapeutic strategies for the progressively aging population of the industrial countries

Development of a high-resolution NGS-based HLA-typing and analysis pipeline

The human leukocyte antigen (HLA) complex contains the most polymorphic genes in the human genome. The classical HLA class I and II genes define the specificity of adaptive immune responses. Genetic variation at the HLA genes is associated with susceptibility to autoimmune and infectious diseases and plays a major role in transplantation medicine and immunology. Currently, the HLA genes are characterized using Sanger- or next-generation sequencing (NGS) of a limited amplicon repertoire or labeled oligonucleotides for allele-specific sequences. High-quality NGS-based methods are in proprietary use and not publicly available. Here, we introduce the first highly automated open-kit/open-source HLA-typing method for NGS. The method employs in-solution targeted capturing of the classical class I (HLA-A, HLA-B, HLA-C) and class II HLA genes (HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1). The calling algorithm allows for highly confident allele-calling to three-field resolution (cDNA nucleotide variants). The method was validated on 357 commercially available DNA samples with known HLA alleles obtained by classical typing. Our results showed on average an accurate allele call rate of 0.99 in a fully automated manner, identifying also errors in the reference data. Finally, our method provides the flexibility to add further enrichment target regions