The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference

The response characteristics of the 6 minute walk test (6MWT) in studies of idiopathic pulmonary fibrosis (IPF) are only poorly understood, and the change in walk distance that constitutes the minimum important difference (MID) over time is unknown

The Power of Brane-Induced Gravity

We study the role of the brane-induced graviton kinetic term in theories with large extra dimensions. In five dimensions we construct a model with a TeV-scale fundamental Planck mass and a {\it flat} extra dimension the size of which can be astronomically large. 4D gravity on the brane is mediated by a massless zero-mode, whereas the couplings of the heavy Kaluza-Klein modes to ordinary matter are suppressed. The model can manifest itself through the predicted deviations from Einstein theory in long distance precision measurements of the planetary orbits. The bulk states can be a rather exotic form of dark matter, which at sub-solar distances interact via strong 5D gravitational force. We show that the induced term changes dramatically the phenomenology of sub-millimeter extra dimensions. For instance, high-energy constraints from star cooling or cosmology can be substantially relaxed.Comment: 24 pages, 4 eps figures; v2 typos corrected; v3 1 ref. added; PRD versio

Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. In addition, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells, and T cell subsets, especially regulatory T cell populations. By contrast, the functions of NRP2 in immune cells are less well known. In this review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications

Bounding the mass of the graviton using gravitional-wave observations of inspiralling compact binaries

If gravitation is propagated by a massive field, then the velocity of gravitational waves (gravitons) will depend upon their frequency and the effective Newtonian potential will have a Yukawa form. In the case of inspiralling compact binaries, gravitational waves emitted at low frequency early in the inspiral will travel slightly slower than those emitted at high frequency later, modifying the phase evolution of the observed inspiral gravitational waveform, similar to that caused by post-Newtonian corrections to quadrupole phasing. Matched filtering of the waveforms can bound such frequency-dependent variations in propagation speed, and thereby bound the graviton mass. The bound depends on the mass of the source and on noise characteristics of the detector, but is independent of the distance to the source, except for weak cosmological redshift effects. For observations of stellar-mass compact inspiral using ground-based interferometers of the LIGO/VIRGO type, the bound on the graviton Compton wavelength is of the order of $6 \times 10^{12}$ km, about double that from solar-system tests of Yukawa modifications of Newtonian gravity. For observations of super-massive black hole binary inspiral at cosmological distances using the proposed laser interferometer space antenna (LISA), the bound can be as large as $6 \times 10^{16}$ km. This is three orders of magnitude weaker than model-dependent bounds from galactic cluster dynamics.Comment: 8 pages, RevTeX, submitted to Phys. Rev.

The Pioneer anomaly and the holographic scenario

In this paper we discuss the recently obtained relation between the Verlinde's holographic model and the first phenomenological Modified Newtonian dynamics. This gives also a promising possible explanation to the Pioneer anomaly.Comment: 5 pages, Accepted for publication in Astrophysics & Space Scienc

Sequence Specificity of BAL 31 Nuclease for ssDNA Revealed by Synthetic Oligomer Substrates Containing Homopolymeric Guanine Tracts

Background: The extracellular nuclease from Alteromonas espejiana, BAL 31 catalyzes the degradation of single-stranded and linear duplex DNA to 59-mononucleotides, cleaves negatively supercoiled DNA to the linear duplex form, and cleaves duplex DNA in response to the presence of apurinic sites. Principal Findings: In this work we demonstrate that BAL 31 activity is affected by the presence of guanine in singlestranded DNA oligomers. Specifically, nuclease activity is shown to be affected by guanine’s presence in minimal homopolymeric tracts in the middle of short oligomer substrates and also by its presence at the 39 end of ten and twenty base oligomers. GNC rich regions in dsDNA are known to cause a decrease in the enzyme’s nuclease activity which has been attributed to the increased thermal stability of these regions, thus making it more difficult to unwind the strands required for enzyme access. Our results indicate that an additional phenomenon could be wholly or partly responsible for the loss of activity in these GNC rich regions. Thus the presence of a guanine tract per se impairs the enzyme’s functionality, possibly due to the tract’s bulky nature and preventing efficient progression through the active site. Conclusions: This study has revealed that the general purpose BAL 31 nuclease commonly used in molecular genetics exhibits a hithertofore non-characterized degree of substrate specificity with respect to single-stranded DNA (ssDNA

Constraints from orbital motions around the Earth of the environmental fifth-force hypothesis for the OPERA superluminal neutrino phenomenology

It has been recently suggested by Dvali and Vikman that the superluminal neutrino phenomenology of the OPERA experiment may be due to an environmental feature of the Earth, naturally yielding a long-range fifth force of gravitational origin whose coupling with the neutrino is set by the scale M_*, in units of reduced Planck mass. Its characteristic length lambda should not be smaller than one Earth's radius R_e, while its upper bound is expected to be slightly smaller than the Earth-Moon distance (60 R_e). We analytically work out some orbital effects of a Yukawa-type fifth force for a test particle moving in the modified field of a central body. Our results are quite general since they are not restricted to any particular size of lambda; moreover, they are valid for an arbitrary orbital configuration of the particle, i.e. for any value of its eccentricity $e$. We find that the dimensionless strength coupling parameter alpha is constrained to |alpha| <= 1 10^-10-4 10^-9 for 1 R_e <= lambda <= 10 R_e by the laser data of the Earth's artificial satellite LAGEOS II, corresponding to M_* >= 4 10^9 -1.6 10^10. The Moon perigee allows to obtain |alpha| <= 3 10^-11 for the Earth-Moon pair in the range 15 R_e <= lambda = 3 10^10 - 4.5 10^10. Our results are neither necessarily limited to the superluminal OPERA scenario nor to the Dvali-Vikman model, in which it is M_* = 10^-6 at lambda = 1 R_e, in contrast with our bounds: they generally extend to any theoretical scenario implying a fifth-force of Yukawa-type.Comment: LaTex2e, 18 pages, 4 figures, 1 table, 81 reference

Post-Einsteinian tests of linearized gravitation

The general relativistic treatment of gravitation can be extended by preserving the geometrical nature of the theory but modifying the form of the coupling between curvature and stress tensors. The gravitation constant is thus replaced by two running coupling constants which depend on scale and differ in the sectors of traceless and traced tensors. When calculated in the solar system in a linearized approximation, the metric is described by two gravitation potentials. This extends the parametrized post-Newtonian (PPN) phenomenological framework while allowing one to preserve compatibility with gravity tests performed in the solar system. Consequences of this extension are drawn here for phenomena correctly treated in the linear approximation. We obtain a Pioneer-like anomaly for probes with an eccentric motion as well as a range dependence of Eddington parameter $\gamma$ to be seen in light deflection experiments.Comment: 15 pages. Accepted version, to appear in Classical and Quantum Gravit

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON