SU(N)-Gauge Theories in Polyakov Gauge on the Torus

We investigate the Abelian projection with respect to the Polyakov loop operator for SU(N) gauge theories on the four torus. The gauge fixed $A_0$ is time-independent and diagonal. We construct fundamental domains for $A_0$. In sectors with non-vanishing instanton number such gauge fixings are always singular. The singularities define the positions of magnetically charged monopoles, strings or walls. These magnetic defects sit on the Gribov horizon and have quantized magnetic charges. We relate their magnetic charges to the instanton number.Comment: 11 pages, 2 figure

Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis

Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively.status: publishe

Historical Improvement in Speed Skating Economy

Half the improvement in 1500-m speed-skating world records can be explained by technological innovations and the other half by athletic improvement. It is hypothesized that improved skating economy is accountable for much of the athletic improvement. Purpose - To determine skating economy in contemporary athletes and to evaluate the change in economy over the years. Methods - Contemporary skaters of the Dutch national junior team (n=8) skated 3 bouts of 6 laps at submaximal velocity, from which skating economy was calculated (in mL O2·kg-1·km-1). A literature search provided historic data of skating velocity and submaximal VO2 (in mL·kg-1·min-1), from which skating economy was determined. The association between year and skating economy was determined using linear regression analysis. Correcting the change in economy for technological innovations resulted in an estimate of the association between year and economy due to athletic improvement. Results An average (±SD) skating economy of 73.4±6.4 mL O2·kg-1·km-1 was found in contemporary athletes. Skating economy improved significantly over the historical timeframe (-0.57 mL O2·kg-1·km-1 per year, 95% confidence interval [-0.84, -0.31]). In the final regression model for the klapskate era, with altitude as confounder, skating economy improved with a non-significant -0.58 mL O2·kg-1·km-1 each year ([-1.19, 0.035]). Conclusions Skating economy was 73.4±6.4 mL O2·kg-1·km-1 in contemporary athletes and improved over the past ~50 years. The association between year and skating economy due to athletic improvement, for the klapskate era, approached significance, suggesting a possible improvement in economy over these years

Neurophysiological effects of human-derived pathological tau conformers in the APPKM670/671NL.PS1/L166P amyloid mouse model of Alzheimer's disease

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by two main pathological hallmarks: amyloid plaques and intracellular tau neurofibrillary tangles. However, a majority of studies focus on the individual pathologies and seldom on the interaction between the two pathologies. Herein, we present the longitudinal neuropathological and neurophysiological effects of a combined amyloid-tau model by hippocampal seeding of human-derived tau pathology in the APP.PS1/L166P amyloid animal model. We statistically assessed both neurophysiological and pathological changes using linear mixed modelling to determine if factors such as the age at which animals were seeded, genotype, seeding or buffer, brain region where pathology was quantified, and time-post injection differentially affect these outcomes. We report that AT8-positive tau pathology progressively develops and is facilitated by the amount of amyloid pathology present at the time of injection. The amount of AT8-positive tau pathology was influenced by the interaction of age at which the animal was injected, genotype, and time after injection. Baseline pathology-related power spectra and Higuchi Fractal Dimension (HFD) score alterations were noted in APP.PS1/L166P before any manipulations were performed, indicating a baseline difference associated with genotype. We also report immediate localized hippocampal dysfunction in the electroencephalography (EEG) power spectra associated with tau seeding which returned to comparable levels at 1 month-post-injection. Longitudinal effects of seeding indicated that tau-seeded wild-type mice showed an increase in gamma power earlier than buffer control comparisons which was influenced by the age at which the animal was injected. A reduction of hippocampal broadband power spectra was noted in tau-seeded wild-type mice, but absent in APP.PS1 animals. HFD scores appeared to detect subtle effects associated with tau seeding in APP.PS1 animals, which was differentially influenced by genotype. Notably, while tau histopathological changes were present, a lack of overt longitudinal electrophysiological alterations was noted, particularly in APP.PS1 animals that feature both pathologies after seeding, reiterating and underscoring the difficulty and complexity associated with elucidating physiologically relevant and translatable biomarkers of Alzheimer's Disease at the early stages of the disease

Quark zero modes in intersecting center vortex gauge fields

The zero modes of the Dirac operator in the background of center vortex gauge field configurations in $\R^2$ and $\R^4$ are examined. If the net flux in D=2 is larger than 1 we obtain normalizable zero modes which are mainly localized at the vortices. In D=4 quasi-normalizable zero modes exist for intersecting flat vortex sheets with the Pontryagin index equal to 2. These zero modes are mainly localized at the vortex intersection points, which carry a topological charge of $\pm 1/2$. To circumvent the problem of normalizability the space-time manifold is chosen to be the (compact) torus \T^2 and \T^4, respectively. According to the index theorem there are normalizable zero modes on \T^2 if the net flux is non-zero. These zero modes are localized at the vortices. On \T^4 zero modes exist for a non-vanishing Pontryagin index. As in $\R^4$ these zero modes are localized at the vortex intersection points.Comment: 20 pages, 4 figures, LaTeX2e, references added, treatment of ideal vortices on the torus shortene

Instantons and Gribov Copies in the Maximally Abelian Gauge

We calculate the Faddeev-Popov operator corresponding to the maximally Abelian gauge for gauge group SU(N). Specializing to SU(2) we look for explicit zero modes of this operator. Within an illuminating toy model (Yang-Mills mechanics) the problem can be completely solved and understood. In the field theory case we are able to find an analytic expression for a normalizable zero mode in the background of a single `t Hooft instanton. Accordingly, such an instanton corresponds to a horizon configuration in the maximally Abelian gauge. Possible physical implications are discussed.Comment: 31 pages, 8 figures, v3: references adde

Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats

Spondyloarthritis (SpA) does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m transgenic rats [120-4 × 283-2]F1, and wild-type rats to test our hypothesis that SpA may be primarily driven by the innate immune response. In vitro, splenocytes were stimulated with heat-inactivated Mycobacterium tuberculosis and cytokine expression and production was measured. In vivo, male and female rats were immunized with 30, 60, or 90 µg of heat-inactivated M. tuberculosis and clinically monitored for spondylitis and arthritis development. After validation of the model, we tested whether prophylactic and therapeutic TNF targeting affected spondylitis and arthritis. In vitro stimulation with heat-inactivated M. tuberculosis strongly induced gene expression of pro-inflammatory cytokines such as TNF, IL-6, IL-1α, and IL-1β, in the HLA-B27 transgenic rats compared with controls. In vivo immunization induced an increased spondylitis and arthritis incidence and an accelerated and synchronized onset of spondylitis and arthritis in HLA-B27 transgenic males and females. Moreover, immunization overcame the protective effect of orchiectomy. Prophylactic TNF targeting resulted in delayed spondylitis and arthritis development and reduced arthritis severity, whereas therapeutic TNF blockade did not affect spondylitis and arthritis severity. Collectively, these data indicate that innate immune activation plays a role in the initiation of HLA-B27-associated disease and allowed to establish a useful in vivo model to study the cellular and molecular mechanisms of disease initiation and progression

Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. Results. Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Pan- eth cells. IL-92positive mononuclear cells were demon- strated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimula- tion of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of a-defensin 5 and IL-23p19. Peripheral and synovial expansion of a4b71 Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. Conclusion. Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA