Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

IntroductionTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA.MethodsMTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial.ResultsOf 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed.ConclusionsTreatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA.Trial registration numberNCT01039688; Results

Highly efficient room temperature spin injection in a metal-insulator-semiconductor light emitting diode

We demonstrate highly efficient spin injection at low and room temperature in an AlGaAs/GaAs semiconductor heterostructure from a CoFe/AlOx tunnel spin injector. We use a double-step oxide deposition for the fabrication of a pinhole-free AlOx tunnel barrier. The measurements of the circular polarization of the electroluminescence in the Oblique Hanle Effect geometry reveal injected spin polarizations of at least 24% at 80K and 12% at room temperature

Quantitative Study of Magnetotransport through a (Ga,Mn)As Single Ferromagnetic Domain

We have performed a systematic investigation of the longitudinal and transverse magnetoresistance of a single ferromagnetic domain in (Ga,Mn)As. We find that, by taking into account the intrinsic dependence of the resistivity on the magnetic induction, an excellent agreement between experimental results and theoretical expectations is obtained. Our findings provide a detailed and fully quantitative validation of the theoretical description of magnetotransport through a single ferromagnetic domain. Our analysis furthermore indicates the relevance of magneto-impurity scattering as a mechanism for magnetoresistance in (Ga,Mn)As.Comment: 5 pages, 4 figures; v2: missing references included, figures recompressed to improve readabilit

Electrical Spin Injection in a Ferromagnetic / Tunnel Barrier/ Semiconductor Heterostructure

We demonstrate experimentally the electrical ballistic electron spin injection from a ferromagnetic metal / tunnel barrier contact into a semiconductor III-V heterostructure. We introduce the Oblique Hanle Effect technique for reliable optical measurement of the degree of injected spin polarization. In a CoFe / Al2O3 / GaAs / (Al,Ga)As heterostructure we observed injected spin polarization in excess of 8 % at 80K.Comment: 5 pages, 4 figure

Local freedom in the gravitational field

In a cosmological context, the electric and magnetic parts of the Weyl tensor, E_{ab} and H_{ab}, represent the locally free curvature - i.e. they are not pointwise determined by the matter fields. By performing a complete covariant decomposition of the derivatives of E_{ab} and H_{ab}, we show that the parts of the derivative of the curvature which are locally free (i.e. not pointwise determined by the matter via the Bianchi identities) are exactly the symmetrised trace-free spatial derivatives of E_{ab} and H_{ab} together with their spatial curls. These parts of the derivatives are shown to be crucial for the existence of gravitational waves.Comment: New results on gravitational waves included; new references added; revised version (IOP style) to appear Class. Quantum Gra

Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid.

All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E-cadherin/catenin complex was shown to be the most probable mechanism of the anti-invasive action. We did a series of experiments to determine whether the anti-invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF-I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action

Integrability of irrotational silent cosmological models

We revisit the issue of integrability conditions for the irrotational silent cosmological models. We formulate the problem both in 1+3 covariant and 1+3 orthonormal frame notation, and show there exists a series of constraint equations that need to be satisfied. These conditions hold identically for FLRW-linearised silent models, but not in the general exact non-linear case. Thus there is a linearisation instability, and it is highly unlikely that there is a large class of silent models. We conjecture that there are no spatially inhomogeneous solutions with Weyl curvature of Petrov type I, and indicate further issues that await clarification.Comment: Minor corrections and improvements; 1 new reference; to appear Class. Quantum Grav.; 16 pages Ioplpp

Polarization tomography of metallic nanohole arrays

We report polarization tomography experiments on metallic nanohole arrays with square and hexagonal symmetry. As a main result, we find that a fully polarized input beam is partly depolarized after transmission through a nanohole array. This loss of polarization coherence is found to be anisotropic, i.e. it depends on the polarization state of the input beam. The depolarization is ascribed to a combination of two factors: i) the nonlocal response of the array due to surface plasmon propagation, ii) the non-plane wave nature of a practical input beam.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Nonperturbative gravito-magnetic fields

In a cold matter universe, the linearized gravito-magnetic tensor field satisfies a transverse condition (vanishing divergence) when it is purely radiative. We show that in the nonlinear theory, it is no longer possible to maintain the transverse condition, since it leads to a non-terminating chain of integrability conditions. These conditions are highly restrictive, and are likely to hold only in models with special symmetries, such as the known Bianchi and $G_2$ examples. In models with realistic inhomogeneity, the gravito-magnetic field is necessarily non-transverse at second and higher order.Comment: Minor changes to match published version; to appear in Phys. Rev.

The properties of the inner disk around HL Tau: Multi-wavelength modeling of the dust emission

We conducted a detailed radiative transfer modeling of the dust emission from the circumstellar disk around HL Tau. The goal of our study is to derive the surface density profile of the inner disk and its structure. In addition to the Atacama Large Millimeter/submillimeter Array images at Band 3 (2.9mm), Band 6 (1.3mm), and Band 7 (0.87mm), the most recent Karl G. Jansky Very Large Array (VLA) observations at 7mm were included in the analysis. A simulated annealing algorithm was invoked to search for the optimum model. The radiative transfer analysis demonstrates that most radial components (i.e., >6AU) of the disk become optically thin at a wavelength of 7mm, which allows us to constrain, for the first time, the dust density distribution in the inner region of the disk. We found that a homogeneous grain size distribution is not sufficient to explain the observed images at different wavelengths simultaneously, while models with a shallower grain size distribution in the inner disk work well. We found clear evidence that larger grains are trapped in the first bright ring. Our results imply that dust evolution has already taken place in the disk at a relatively young (i.e., ~1Myr) age. We compared the midplane temperature distribution, optical depth, and properties of various dust rings with those reported previously. Using the Toomre parameter, we briefly discussed the gravitational instability as a potential mechanism for the origin of the dust clump detected in the first bright ring via the VLA observations.Comment: Accepted for publication in A&A (10 pages