Lattice perturbation theory for gluonic and fermionic actions

We calculate the two loop Landau mean links and the one loop renormalisation of the anisotropy for Wilson and improved SU(3) gauge actions, using twisted boundary conditions as a gauge invariant infrared regulator. We show these accurately describe simulated results, and outline a method for generating Feynman rules for general lattice field theories, in a form suitable for efficient numerical calculation of perturbative loop diagrams.Comment: 6 pages of LaTeX. Two posters at Lattice2002(improve) combine

The Use of Serum Glial Fibrillary Acidic Protein Measurements in the Diagnosis of Neuromyelitis Optica Spectrum Optic Neuritis

Background: Glial fibrillary acidic protein (GFAP) is a specific intermediate filament of the cytoskeleton of the astrocyte and may be used as a specific marker for astrocytic damage. It is detectable in the cerebrospinal fluid following a relapse caused by Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) spectrum disease. Higher levels are found following an NMO-related relapse. It is not known if GFAP is also detectable in the serum following such relapses. In particular, it is not known if lesions limited to the optic nerve release GFAP in sufficient quantities to be detectable within the serum. The aim of this study was to ascertain the extent to which serum GFAP levels can distinguish between an episode of optic neuritis (ON) related to NMO spectrum disease and ON from other causes.Methodology/Principal Findings: Out of 150 patients consecutively presenting to our eye hospital over the period March 2009 until July 2010, we were able to collect a serum sample from 12 patients who had presented with MS-related ON and from 10 patients who had presented with NMO spectrum disease-related ON. We also identified 8 patients with recurrent isolated ON and 8 patients with a corticosteroid-dependent optic neuropathy in the absence of any identified aetiology. GFAP was detectable in the serum of all but three patients (two patients with MS-related ON and one with recurrent optic neuritis). The median serum GFAP level in the patient group with NMO spectrum disease was 4.63 pg/mL whereas in all other cases combined together, this was 2.14 pg/mL. The difference was statistically significant (P = 0.01). A similar statistically significant difference was found when cases with pathology limited to the optic nerve were compared (P = 0.03).Conclusions: Glial pathology in NMO related optic neuritis is reflected in elevated serum GFAP levels independently of whether or not there is extra-optic nerve disease

The contribution of O(alpha) radiative corrections to the renormalised anisotropy and application to general tadpole improvement schemes: addendum to "One loop calculation of the renormalised anisotropy for improved anisotropic gluon actions on a lattice" [hep-lat/0208010]

General O(alpha) radiative corrections to lattice actions may be interpreted as counterterms that give additive contributions to the one-loop renormalisation of the anisotropy. The effect of changing the radiative coefficients is thus easily calculable. In particular, the results obtained in a previous paper for Landau mean link improved actions apply in any tadpole improvement scheme. We explain how this method can be exploited when tuning radiatively improved actions. Efficient methods for self-consistently tuning tadpole improvement factors are also discussed.Comment: 3 pages of revte

Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.

The archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp interacts with a host of DNA modifying enzymes, providing a stable anchorage and enhancing their respective processivities. Given the broad range of enzymes with which PCNA has been shown to interact, relatively little is known about the mode of assembly of functionally meaningful combinations of enzymes on the PCNA clamp. We have determined the X-ray crystal structure of the Sulfolobus solfataricus PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at 2.9 A resolution. We demonstrate the specificity of interaction of the PCNA subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a rationale for the specific interaction of the C-terminal PIP-box motif of FEN1 for the PCNA1 subunit. The structure explains the specificity of the individual archaeal PCNA subunits for selected repair enzyme 'clients', and provides insights into the co-ordinated assembly of sequential enzymatic steps in PCNA-scaffolded DNA repair cascades

Automatically generating Feynman rules for improved lattice field theories

Deriving the Feynman rules for lattice perturbation theory from actions and operators is complicated, especially when improvement terms are present. This physically important task is, however, suitable for automation. We describe a flexible algorithm for generating Feynman rules for a wide range of lattice field theories including gluons, relativistic fermions and heavy quarks. We also present an efficient implementation of this in a freely available, multi-platform programming language (\python), optimised to deal with a wide class of lattice field theories

Osteogenesis Imperfecta:New Insights into Extraskeletal Complications

This thesis aims at expanding our understanding of Osteogenesis Imperfecta (OI), a genetic disorder causing bone fragility and a range of extraskeletal symptoms. The work examines in particular the epidemiology and the extraskeletal comorbidities of the Dutch OI population. Additionally, the thesis sheds light on the genotype-phenotype correlation and the pathophysiology of the respiratory complications associated with OI. The first part of the thesis discusses the prevalence and hospital admission rates of the Dutch OI population, the genotype-phenotype relation of OI, and the health care characteristics of patients with LRP5, PLS3, or WNT1 pathogenic variants. The second part of the thesis focuses on the pulmonary complications of OI patients. A literature review provides an overview of the current knowledge and knowledge gaps surrounding the pathophysiology of respiratory complications in OI. To gain further insight into the cause of pulmonary complications, the lung pathology in patients with OI type II was analyzed, suggesting intrinsic alterations in the OI lung parenchyma. The second part of this thesis concludes by proposing a more patient-friendly lung function assessment and a pulmonary follow-up plan for OI patients for the prevention of serious respiratory complications. Finally, the third part of the thesis provides an overview of collagen regulation in the context of recent gene discoveries and describes two OI patient with new SPARC pathogenic variants

Perturbation theory vs. simulation for tadpole improvement factors in pure gauge theories

We calculate the mean link in Landau gauge for Wilson and improved SU(3) anisotropic gauge actions, using two loop perturbation theory and Monte Carlo simulation employing an accelerated Langevin algorithm. Twisted boundary conditions are employed, with a twist in all four lattice directions considerably improving the (Fourier accelerated) convergence to an improved lattice Landau gauge. Two loop perturbation theory is seen to predict the mean link extremely well even into the region of commonly simulated gauge couplings and so can be used remove the need for numerical tuning of self-consistent tadpole improvement factors. A three loop perturbative coefficient is inferred from the simulations and is found to be small. We show that finite size effects are small and argue likewise for (lattice) Gribov copies and double Dirac sheets.Comment: 13 pages of revtex

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists