Compositions, Methods And Kits Relating To Thrombin Degradation Resistant Fibroblast Growth Factor-1

The invention relates to novel degradation resistant FGF-1, and methods for producing and using the same. More specifically, the invention relates to identification of a thrombin degradation resistant FGF-1, an a nucleic acid encoding the same. The thrombin degradation resistant FGF-1 can elicit responses that are otherwise typically impeded by degradation of FGF-1 by thrombin. Thrombin degradation resistant FGF-1 is an important molecule for effecting an FGF-1 response that would be otherwise inhibited by thrombin. Thus, the present invention provides a powerful therapeutic for diseases or disorders wherein an FGF-1 response can mediate a reduction in the frequency or intensity of a symptom of the disease or disorder but for degradation of FGF-1 before it can effect the response

Tensors, non-Gaussianities, and the future of potential reconstruction

We present projections for reconstruction of the inflationary potential expected from ESA's upcoming Planck Surveyor CMB mission. We focus on the effects that tensor perturbations and the presence of non-Gaussianities have on reconstruction efforts in the context of non-canonical inflation models. We consider potential constraints for different combinations of detection/null-detection of tensors and non-Gaussianities. We perform Markov Chain Monte Carlo and flow analyses on a simulated Planck-precision data set to obtain constraints. We find that a failure to detect non-Gaussianities precludes a successful inversion of the primordial power spectrum, greatly affecting uncertainties, even in the presence of a tensor detection. In the absence of a tensor detection, while unable to determine the energy scale of inflation, an observable level of non-Gaussianities provides correlations between the errors of the potential parameters, suggesting that constraints might be improved for suitable combinations of parameters. Constraints are optimized for a positive detection of both tensors and non-Gaussianities.Comment: 12 pages, 5 figures, LaTeX; V2: version submitted to JCA

The Lyth Bound and the End of Inflation

We derive an extended version of the well-known Lyth Bound on the total variation of the inflaton field, incorporating higher order corrections in slow roll. We connect the field variation $\Delta\phi$ to both the spectral index of scalar perturbations and the amplitude of tensor modes. We then investigate the implications of this bound for ``small field'' potentials, where the field rolls off a local maximum of the potential. The total field variation during inflation is {\em generically} of order $m_{\rm Pl}$, even for potentials with a suppressed tensor/scalar ratio. Much of the total field excursion arises in the last e-fold of inflation and in single field models this problem can only be avoided via fine-tuning or the imposition of a symmetry. Finally, we discuss the implications of this result for inflationary model building in string theory and supergravity.Comment: 10 pages, RevTeX, 2 figures (V3: version accepted for publication by JCAP

Novel fibrin-fibronectin matrix accelerates mice skin wound healing

Plasma fibrinogen (F1) and fibronectin (pFN) polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing. About 90% of plasma F1 has a homodimeric pair of γ chains (γγF1), and 10% has a heterodimeric pair of γ and more acidic γ′ chains (γγ′F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of γγ′F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII (rFXIIIa). In this matrix, the fibrin nanofibers were decorated with pFN nanoclusters (termed γγ′F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of γγF1 and pFN formed a sporadic dis- tribution of “pFN droplets” (termed γγF1+pFN fibrin). The γγ′F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the γγF1+FN fibrin. Three dimensional (3D) culturing showed that the γγ′F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D γγ′F1:pFN fibrin exhibited a starkly enhanced vascular mor- phogenesis while an apoptotic growth profile was observed in the γγF1+pFN fibrin. Relative to γγF1+pFN fibrin, mouse dermal wounds that were sealed by γγ′F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing