Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily involving the synovium. Evidence in recent years has suggested that the bone marrow (BM) may be involved, and may even be the initiating site of the disease. Abnormalities in haemopoietic stem cells' (HSC) survival, proliferation and aging have been described in patients affected by RA and ascribed to abnormal support by the BM microenvironment. Mesenchymal stem cells (MSC) and their progeny constitute important components of the BM niche. In this study we test the hypothesis that the onset of inflammatory arthritis is associated with altered self-renewal and differentiation of bone marrow MSC, which alters the composition of the BM microenvironment. Methods: We have used Balb/C Interleukin-1 receptor antagonist knock-out mice, which spontaneously develop RA-like disease in 100% of mice by 20 weeks of age to determine the number of mesenchymal progenitors and their differentiated progeny before, at the start and with progression of the disease. Results: We showed a decrease in the number of mesenchymal progenitors with adipogenic potential and decreased bone marrow adipogenesis before disease onset. This is associated with a decrease in osteoclastogenesis. Moreover, at the onset of disease a significant increase in all mesenchymal progenitors is observed together with a block in their differentiation to osteoblasts. This is associated with accelerated bone loss. Conclusions: Significant changes occur in the BM niche with the establishment and progression of RA-like disease. Those changes may be responsible for aspects of the disease, including the advance of osteoporosis. An understanding of the molecular mechanisms leading to those changes may lead to new strategies for therapeutic intervention

Finite size scaling in the 2D XY-model and generalized universality

In recent works (BHP), a generalized universality has been proposed, linking phenomena as dissimilar as 2D magnetism and turbulence. To test these ideas, we performed a MC study of the 2D XY-model. We found that the shape of the probability distribution function for the magnetization M is non Gaussian and independent of the system size --in the range of the lattice sizes studied-- below the Kosterlitz-Thoules temperature. However, the shape of these distributions does depend on the temperature, contrarily to the BHP's claim. This behavior is successfully explained by using an extended finite-size scaling analysis and the existence of bounds for M.Comment: 7 pages, 5 figures. Submitted to Phys. Rev. Lett. Details of changes: 1. We emphasized in the abstract the range of validity of our results. 2. In the last paragraph the temperature dependence of the PDF was slightly re-formulate

Stability of Fine Tuned Hierarchies in Strongly Coupled Chiral Models

A fine tuned hierarchy between a strongly coupled high energy compositeness scale and a much lower chiral symmetry breaking scale is a requisite ingredient in many models of dynamical electroweak symmetry breaking. Using a nonperturbative continuous Wilson renormalization group equation approach, we explore the stability of such a hierarchy against quantum fluctuations.Comment: 14,PURD-TH-94-1

On the Holomorphic Structure of a Low Energy Supersymmetric Wilson Effective Action

The Wilson (exact) renormalization group equations are used to determine the evolution of a general low energy N=1 supersymmetric action containing a U(1) gauge vector multiplet and a neutral chiral multiplet. The effective theory evolves towards satisfying a fixed relation where the K\"ahler potential and effective gauge coupling are obtained from a N=2 supersymmetric holomorphic prepotential.Comment: 10 pages, LaTe

Development of real-time PCR and hybridization methods for detection and identification of thermophilic Campylobacter spp. in pig faecal samples

Aims: To develop a real-time (rt) PCR for species differentiation of thermophilic Campylobacter and to develop a method for assessing co-colonization of pigs by Campylobacter spp. Methods and results: The specificity of a developed 5’nuclease rt-PCR for species-specific identification of C. jejuni, C. coli, C. lari, C. upsaliensis and of a hipO gene nucleotide probe for detection of C. jejuni by colony-blot hybridization were determined by testing a total of 75 reference strains of Campylobacter spp. and related organisms. The rt-PCR method allowed species-specific detection of Campylobacter spp. in naturally infected pig faecal samples after an enrichment step, whereas the hybridization approach enhanced the specific isolation of C. jejuni (present in minority to C. coli) from pigs. Conclusions: The rt-PCR was specific for Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis and the colony-blot hybridization approach provided an effective tool for isolation of C. jejuni from pig faecal samples typically dominated by C. coli. Significance and impact of study: Species differentiation between thermophilic Campylobacter is difficult by phenotypic methods and the developed rt-PCR provides an easy and fast method for such differentiation. Detection of C. jejuni by colony hybridization may increase the isolation rate of this species from pig feces

Wilson Renormalization Group Analysis of Theories with Scalars and Fermions

The continuous block spin (Wilson) renormalization group equation governing the scale dependence of the action is constructed for theories containing scalars and fermions. A locally approximated form of this equation detailing the structure of a generalized effective potential is numerically analyzed. The role of the irrelevant operators in the nonperturbative renormalization group running is elucidated and a comparison with the 1-loop perturbative results is drawn. Focusing on the spontaneously broken phase of a model possessing a discrete symmetry forbidding an explicit fermion mass term, mass bounds on both the scalar and fermion degrees of freedom are established. The effect of the generalized Yukawa coupling on the scalar mass upper bound is emphasized.Comment: 40, PURD-TH-92-

Two spatially distinct posterior alpha sources fulfill different functional roles in attention

Directing attention helps extracting relevant information and suppressing distracters. Alpha brain oscillations (8-12Hz) are crucial for this process, with power decreases facilitating processing of important information and power increases inhibiting brain regions processing irrelevant information. Evidence for this phenomenon arises from visual attention studies (Worden et al., 2000b), however, the effect also exists in other modalities, including the somatosensory system (Haegens et al., 2011) and inter-sensory attention tasks (Foxe and Snyder, 2011). We investigated in human participants (10 females, 10 males) the role of alpha oscillations in focused (0/100%) vs. divided (40/60%) attention, both across modalities (visual/somatosensory; Experiment 1) and within the same modality (visual domain: across hemifields; Experiment 2) while recording EEG over 128 scalp electrodes. In Experiment 1 participants divided their attention between visual and somatosensory modality to determine the temporal/spatial frequency of a target stimulus (vibrotactile stimulus/Gabor grating). In Experiment 2, participants divided attention between two visual hemifields to identify the orientation of a Gabor grating. In both experiments, pre-stimulus alpha power in visual areas decreased linearly with increasing attention to visual stimuli. In contrast, pre-stimulus alpha power in parietal areas was lower when attention was divided between modalities/hemifields, compared to focused attention. These results suggest there are two alpha sources, where one reflects the ‘visual spotlight of attention’ and the other reflects attentional effort. To our knowledge, this is the first study to show that attention recruits two spatially distinct alpha sources in occipital and parietal brain regions, acting simultaneously but serving different functions in attention

Cost-effectiveness analysis of recombinant factor VIII Fc-fusion protein (rFVIIIFc) for the treatment of severe hemophilia A in Italy incorporating real-world dosing and joint health data

Background Patients with severe hemophilia A (SHA) in Italy are routinely treated with standard half-life recombinant factor VIII (rFVIII) products. rFVIII Fc-fusion protein (rFVIIIFc) is an extended half-life rFVIII product that enables less frequent administration than rFVIII, which may support improved adherence. Available data indicate low breakthrough bleed rates and potentially improved long-term joint health for patients treated with rFVIIIFc prophylaxis. Objective This study assessed the cost effectiveness of rFVIIIFc versus rFVIII from an Italian healthcare perspective. Methods A Semi-Markov model was constructed to assess the lifetime costs and benefits of rFVIII and rFVIIIFc prophylaxis. rFVIII product acquisition costs from a published Italian database were included for both prophylaxis and the resolution of breakthrough bleeding. Clinical outcomes within the model were determined based on published annualized bleeding rates and literature regarding the development of target joints (TJs) as the incidence of bleeds and TJs is associated with impaired health-related quality of life. Cost effectiveness was assessed using cost per quality-adjusted life-year (QALY) gained. Results Compared with rFVIII, rFVIIIFc was associated with a per-patient cost saving of approximately €1.3 million and QALY gains of 0.39 over a lifetime horizon. Sensitivity analyses considering alternative efficacy, dosing, and structural assumptions each showed that rFVIIIFc dominated rFVIII (i.e., provided more QALYs at a reduced cost). Conclusions This cost-effectiveness analysis demonstrated that rFVIIIFc may offer a cost-effective treatment option for patients with SHA in Italy

Sensitivity of an antineutrino monitor for remote nuclear reactor discovery

Antineutrinos from a nuclear reactor comprise an unshieldable signal, which carries information about the core. A gadolinium-doped, water-based Cherenkov detector has been investigated for detection of reactor antineutrinos for midfield remote reactor monitoring for nonproliferation applications. Two independent reconstruction and analysis pathways have been developed and applied to a number of representative reactor signals to evaluate the sensitivity of a kiloton-scale, gadolinium-doped Cherenkov detector as a remote monitor prototype. The sensitivity of four detector configurations to nine reactor signal combinations was evaluated for a detector situated in Boulby Mine, close to the Boulby Underground Laboratory in the UK. It was found that a 22-m detector with a gadolinium-doped, water-based liquid scintillator fill is sensitive to an approximately 3-GWth reactor at a standoff of approximately 150km within 2 years in the current reactor landscape. A larger detector would be required to achieve a more timely detection or to monitor smaller or more distant reactors

Bacterial dimethylsulfoniopropionate degradation genes in the oligotrophic North Pacific subtropical gyre

Dimethylsulfoniopropionate (DMSP) is an organic sulfur compound that is rapidly metabolized by marine bacteria either by cleavage to dimethylsulfide (DMS) or demethylation to 3-methiolpropionate. The abundance and diversity of genes encoding bacterial DMS production (dddP) and demethylation (dmdA) were measured in the North Pacific subtropical gyre (NPSG) between May 2008 and February 2009 at Station ALOHA (22°45=N, 158°00=W) at two depths: 25mand the deep chlorophyll maximum (DCM;~100 m). The highest abundance of dmdA genes was in May 2008 at 25 m, with~16.5% of cells harboring a gene in one of the eight subclades surveyed, while the highest abundance of dddP genes was in July 2008 at 25 m, with~2% of cells harboring a gene. The dmdA gene pool was consistently dominated by homologs from SAR11 subclades, which was supported by findings in metagenomic data sets derived from Station ALOHA. Expression of the SAR11 dmdA genes was low, with typical transcript:gene ratios between 1:350 and 1:1,400. The abundance of DMSP genes was statistically different between 25mand the DCM and correlated with a number of environmental variables, including primary production, photosynthetically active radiation, particulate DMSP, and DMS concentrations. At 25 m, dddP abundance was positively correlated with pigments that are diagnostic of diatoms; at the DCM, dmdA abundance was positively correlated with temperature. Based on gene abundance, we hypothesize that SAR11 bacterioplankton dominate DMSP cycling in the oligotrophic NPSG, with lesser but consistent involvement of other members of the bacterioplankton community