A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset.

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset. METHODS: Twenty-five previously untreated consecutive patients with recent-onset (\u3c 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients. RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR of skin biopsies demonstrated a marked decrease in expression of fibrosis-related genes. CONCLUSION: Patients with diffuse progressive cutaneous SSc of recent onset treated with MMF experienced marked improvement in skin involvement and stabilization of pulmonary function. Skin biopsies from 3 patients demonstrated histopathological improvement and decreased expression of fibrosis-related genes

The star-formation histories of elliptical galaxies across the fundamental plane

We present the first results from a study designed to test whether, given high-quality spectrophotometry spanning the mid-UV--optical wavelength regime, it is possible to distinguish the metal content (Z) and star-formation history (sfh) of individual elliptical galaxies with sufficient accuracy to establish whether their formation history is linked to their detailed morphology and position on the Fundamental Plane. From a detailed analysis of UV-optical spectrophotometry of the `cuspy' elliptical galaxy NGC 3605 and the giant elliptical NGC 5018 we find that: 1) optical spectra with l > 3500 A may not contain sufficient data to robustly uncover all the stellar populations present in individual galaxies, even in such relatively passive objects as ellipticals, 2) the addition of the UV data approaching l = 2500 A holds the key to establishing well-constrained sfhs, from which we can infer a formation and evolution history which is consistent with their photometric properties, 3) despite the superficial similarity of their spectra, the two galaxies have very different `recent' sfhs -- the smaller, cuspy elliptical NGC 3605 contains a high-Z population of age ~= 1 Gyr, and has a position on the fundamental plane typical of the product of a low-z gas-rich merger (most likely at z ~ 0.08), while the giant elliptical NGC 5018, with a sub-solar secondary population, appears to have gained its more recent stars via mass transfer / accretion of gas from its spiral companion, 4) despite these differences in detailed history, more than 85% of the stellar mass of both galaxies is associated with an old (9-12 Gyr) stellar population of near-solar Z. This pilot study provides strong motivation for the construction and analysis of high-quality UV-optical spectra for a substantial sample of ellipticals spanning the Fundamental Plane.Comment: 11 pages, 10 figures, submitted to MNRAS, revised versio

Nitrogen Incorporation in CH_4-N_2 Photochemical Aerosol Produced by Far Ultraviolet Irradiation

Nitrile incorporation into Titan aerosol accompanying hydrocarbon chemistry is thought to be driven by extreme UV wavelengths (λ120 nm is presently unaccounted for in atmospheric photochemical models. We suggest that reaction with CH radicals produced from CH_4 photolysis may provide a mechanism for incorporating N into the molecular structure of the aerosol. Further work is needed to understand the chemistry involved, as these processes may have significant implications for how we view prebiotic chemistry on early Earth and similar planets. Key Words: Titan—Photochemical aerosol—CH_4-N_2 photolysis—Far UV—Nitrogen activation

Neutral current (anti)neutrino scattering: relativistic mean field and superscaling predictions

We evaluate the neutral current quasi-elastic neutrino cross section within two nuclear models: the SuSA model, based on the superscaling behavior of electron scattering data, and the RMF model, based on relativistic mean field theory. We also estimate the ratio $(\nu p \to \nu p)/(\nu N \to \nu N)$ and compare with the MiniBooNE experimental data, performing a fit of the parameters $M_A$ and $g_A^{(s)}$ within the two models. Finally, we present our predictions for antineutrino scattering.Comment: 15 pages, 4 figure

Reactivity of OH and CH3OH between 22 and 64 K: Modelling the gas phase production of CH3O in Barnard 1b

In the last years, ultra-low temperature chemical kinetic experiments have demonstrated that some gas-phase reactions are much faster than previously thought. One example is the reaction between OH and CH3OH, which has been recently found to be accelerated at low temperatures yielding CH3O as main product. This finding opened the question of whether the CH3O observed in the dense core Barnard 1b could be formed by the gas-phase reaction of CH3OH and OH. Several chemical models including this reaction and grain-surface processes have been developed to explain the observed abundance of CH$_3$O with little success. Here we report for the first time rate coefficients for the gas-phase reaction of OH and CH3OH down to a temperature of 22 K, very close to those in cold interstellar clouds. Two independent experimental set-ups based on the supersonic gas expansion technique coupled to the pulsed laser photolysis-laser induced fluorescence technique were used to determine rate coefficients in the temperature range 22-64 K. The temperature dependence obtained in this work can be expressed as k(22-64 K) = (3.6+/-0.1)e-12 (T/ 300)^(-1.0+/-0.2) cm3 molecule-1 s-1. Implementing this expression in a chemical model of a cold dense cloud results in CH3O/CH3OH abundance ratios similar or slightly lower than the value of 3e-3 observed in Barnard 1b. This finding confirms that the gas-phase reaction between OH and CH3OH is an important contributor to the formation of interstellar CH3O. The role of grain-surface processes in the formation of CH3O, although it cannot be fully neglected, remains controversial.Comment: Accepted for publication in The Astrophysical Journa

Comparative analysis of rigidity across protein families

We present a comparative study in which 'pebble game' rigidity analysis is applied to multiple protein crystal structures, for each of six different protein families. We find that the main-chain rigidity of a protein structure at a given hydrogen bond energy cutoff is quite sensitive to small structural variations, and conclude that the hydrogen bond constraints in rigidity analysis should be chosen so as to form and test specific hypotheses about the rigidity of a particular protein. Our comparative approach highlights two different characteristic patterns ('sudden' or 'gradual') for protein rigidity loss as constraints are removed, in line with recent results on the rigidity transitions of glassy networks

Off-shell effects in the relativistic mean field model and their role in CC (anti)neutrino scattering at MiniBooNE kinematics

The relativistic mean field (RMF) model is used to describe nucleons in the nucleus and thereby to evaluate the effects of having dynamically off-shell spinors. Compared with free, on-shell nucleons as employed in some other models, within the RMF nucleons are described by relativistic spinors with strongly enhanced lower components. In this work it is seen that for MiniBooNE kinematics, neutrino charged-current quasielastic cross sections show some sensitivity to these off-shell effects, while for the antineutrino-nucleus case the total cross sections are seen to be essentially independent of the enhancement of the lower components. As was found to be the case when comparing the RMF results with the neutrino-nucleus data, the present impulse approximation predictions within the RMF also fall short of the MiniBooNE antineutrino-nucleus data.Comment: 19 pages, 7 figures, submitted to Physics Letters

Mechanism of NSF: New evidence challenging the prevailing theory

Nephrogenic systemic fibrosis (NSF) has been associated with the administration of gadolinium-based contrast agents in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), or acute renal failure (ARF). Since the vast majority of these patients do not get NSF, it is highly likely that patient factors play a role in its development. Although free or dechelated gadolinium is thought by some to be the only trigger of NSF, recent evidence suggests that chelated gadolinium may be important. Chelated gadolinium such as Omniscan (gadodiamide) and Magnevist (gadopentetate) can directly stimulate macrophages and monocytes in vitro to release profibrotic cytokines and growth factors capable of initiating and supporting the tissue fibrosis that is characteristic of NSF. In addition, an effect of chelated gadolinium on fibroblasts has also been demonstrated. Chelated gadolinium in the form of Omniscan, Magnevist, MultiHance, and ProHance increased proliferation of human dermal fibroblasts. Indeed, increased numbers of macrophages, together with activated fibroblasts and fibrocytes, are essential cells in the fibrotic process and are present in NSF skin. Accordingly, it is important that chelated gadolinium, in combination with patient cofactors, is considered in the etiology of NSF associated with enhanced scans