Dangers of Indiscriminate Antibiotic Use

The introduction of antibiotics into therapy during the past ten years has provided a potent weapon against many diseases. The apparent innocuous nature and low toxicity of these drugs qualified them for the label of miracle drugs. The antibiotics have altered therapeutics to an amazing degree, and have done much in overcoming the dangers of some types of diseases. However, like high powered bullets, they can be dangerous if uncontrolled. Unlike most other drugs, antibiotics do not have a self-limiting cure-or-kill basis, but have ramifications of undesirable effects which may persist to provide health hazards to an alarming degree not only to animals but to persons working with them. In recent years an increasing number of articles have appeared in the scientific literature on hazards associated with indiscriminate widespread use of these potent drugs. While recognizing the undisputed role of antibiotics in present day therapy, the subject of this report is concerned with undesirable effects and an evaluation of what present indiscriminate use of antibiotics can lead to

Modulation of IL-17 and Foxp3 Expression in the Prevention of Autoimmune Arthritis in Mice

©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. Methodology and Findings: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. Conclusions: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.This work was funded by SUDOE, grant number IMMUNONET-SOE1/1P1/E014, and supported by a research grant from Fundação para a Ciência e Tecnologia (FCT), Portugal (FCT/POCI/SAU-MMO/55974/2004). JD, AA-D, and VGO are funded with scholarships from FCT (SFRH/BD/23631/2005, SFRH/BD/49093/2008, and SFRH/BPD/22575/2005)

CMB polarimetry with BICEP: instrument characterization, calibration, and performance

BICEP is a ground-based millimeter-wave bolometric array designed to target the primordial gravity wave signature on the polarization of the cosmic microwave background (CMB) at degree angular scales. Currently in its third year of operation at the South Pole, BICEP is measuring the CMB polarization with unprecedented sensitivity at 100 and 150 GHz in the cleanest available 2% of the sky, as well as deriving independent constraints on the diffuse polarized foregrounds with select observations on and off the Galactic plane. Instrument calibrations are discussed in the context of rigorous control of systematic errors, and the performance during the first two years of the experiment is reviewed.Comment: 12 pages, 15 figures, updated version of a paper accepted for Millimeter and Submillimeter Detectors and Instrumentation for Astronomy IV, Proceedings of SPIE, 7020, 200

Non-isothermal model for the direct isotropic/smectic-A liquid crystalline transition

An extension to a high-order model for the direct isotropic/smectic-A liquid crystalline phase transition was derived to take into account thermal effects including anisotropic thermal diffusion and latent heat of phase-ordering. Multi-scale multi-transport simulations of the non-isothermal model were compared to isothermal simulation, showing that the presented model extension corrects the standard Landau-de Gennes prediction from constant growth to diffusion-limited growth, under shallow quench/undercooling conditions. Non-isothermal simulations, where meta-stable nematic pre-ordering precedes smectic-A growth, were also conducted and novel non-monotonic phase-transformation kinetics observed.Comment: First revision: 20 pages, 7 figure

Absolute polarization angle calibration using polarized diffuse Galactic emission observed by BICEP

We present a method of cross-calibrating the polarization angle of a polarimeter using BICEP Galactic observations. \bicep\ was a ground based experiment using an array of 49 pairs of polarization sensitive bolometers observing from the geographic South Pole at 100 and 150 GHz. The BICEP polarimeter is calibrated to +/-0.01 in cross-polarization and less than +/-0.7 degrees in absolute polarization orientation. BICEP observed the temperature and polarization of the Galactic plane (R.A= 100 degrees ~ 270 degrees and Dec. = -67 degrees ~ -48 degrees). We show that the statistical error in the 100 GHz BICEP Galaxy map can constrain the polarization angle offset of WMAP Wband to 0.6 degrees +\- 1.4 degrees. The expected 1 sigma errors on the polarization angle cross-calibration for Planck or EPIC are 1.3 degrees and 0.3 degrees at 100 and 150 GHz, respectively. We also discuss the expected improvement of the BICEP Galactic field observations with forthcoming BICEP2 and Keck observations.Comment: 13 pages, 10 figures and 2 tables. To appear in Proceedings of SPIE Astronomical Telescopes and Instrumentation 201

Experimental and numerical study of the effects of the reversal hot rolling conditions on the recrystallization behavior of austenite model alloys

The experimental and numerical study of the effects of the recrystallization behavior of austenite model alloys during hot plate rolling on reverse rolling is the main goal of the paper. The computer models that are currently applied for simulation of reverse rolling are not strain-path-sensitive, thus leading to overestimation of the processing parameters outside the accepted process window (e.g., deformation in the partial austenite recrystallization region). Therefore, in this work, a particular focus is put on the investigation of strain path effects that occur during hot rolling and their influence on the microstructure evolution and mechanical properties of microalloyed austenite. Both experimental and numerical techniques are employed in this study, taking advantage of the integrated computational material engineering concept. The combined isotropic–kinematic hardening model is used for the macroscale predictions to take into account softening effects due to strain reversal. The macroscale model is additionally enriched with the full-field microstructure evolution model within the cellular automata framework. Examples of obtained results, highlighting the role of the strain reversal on the microstructural response, are presented within the paper. The combination of the physical simulation of austenitic model alloys and computer modeling provided new insights into optimization of the processing routes of advanced high-strength steels (AHSS)

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Searching for non-Gaussianity in the VSA data

We have tested Very Small Array (VSA) observations of three regions of sky for the presence of non-Gaussianity, using high-order cumulants, Minkowski functionals, a wavelet-based test and a Bayesian joint power spectrum/non-Gaussianity analysis. We find the data from two regions to be consistent with Gaussianity. In the third region, we obtain a 96.7% detection of non-Gaussianity using the wavelet test. We perform simulations to characterise the tests, and conclude that this is consistent with expected residual point source contamination. There is therefore no evidence that this detection is of cosmological origin. Our simulations show that the tests would be sensitive to any residual point sources above the data's source subtraction level of 20 mJy. The tests are also sensitive to cosmic string networks at an rms fluctuation level of $105 \mu K$ (i.e. equivalent to the best-fit observed value). They are not sensitive to string-induced fluctuations if an equal rms of Gaussian CDM fluctuations is added, thereby reducing the fluctuations due to the strings network to $74 \mu K$ rms . We especially highlight the usefulness of non-Gaussianity testing in eliminating systematic effects from our data.Comment: Minor corrections; accepted for publication to MNRA