The Orphan Nuclear Estrogen Receptor–Related Receptor α (Errα) Is Expressed Throughout Osteoblast Differentiation and Regulates Bone Formation in Vitro

The orphan nuclear estrogen receptor–related receptor α (ERRα), is expressed by many cell types, but is very highly expressed by osteoblastic cells in which it transactivates at least one osteoblast-associated gene, osteopontin. To study the putative involvement of ERRα in bone, we first assessed its expression in rat calvaria (RC) in vivo and in RC cells in vitro. ERRα mRNA and protein were expressed at all developmental stages from early osteoprogenitors to bone-forming osteoblasts, but protein was most abundant in mature cuboidal osteoblasts. To assess a functional role for ERRα in osteoblast differentiation and bone formation, we blocked its expression by antisense oligonucleotides in either proliferating or differentiating RC cell cultures and found inhibition of cell growth and a proliferation-independent inhibition of differentiation. On the other hand, ERRα overexpression in RC cells increased differentiation and maturation of progenitors to mature bone-forming cells. Our findings show that ERRα is highly expressed throughout the osteoblast developmental sequence and plays a physiological role in differentiation and bone formation at both proliferation and differentiation stages. In addition, we found that manipulation of receptor levels in the absence of known ligand is a fruitful approach for functional analysis of this orphan receptor and identification of potential target genes

Secure Vehicular Communication Systems: Implementation, Performance, and Research Challenges

Vehicular Communication (VC) systems are on the verge of practical deployment. Nonetheless, their security and privacy protection is one of the problems that have been addressed only recently. In order to show the feasibility of secure VC, certain implementations are required. In [1] we discuss the design of a VC security system that has emerged as a result of the European SeVeCom project. In this second paper, we discuss various issues related to the implementation and deployment aspects of secure VC systems. Moreover, we provide an outlook on open security research issues that will arise as VC systems develop from today's simple prototypes to full-fledged systems

Nonstoichiometric doping and Bi antisite defect in single crystal Bi2Se3

We studied the defects of Bi2Se3 generated from Bridgman growth of stoichiometric and nonstoichiometric self-fluxes. Growth habit, lattice size, and transport properties are strongly affected by the types of defect generated. Major defect types of Bi_Se antisite and partial Bi_2-layer intercalation are identified through combined studies of direct atomic-scale imaging with scanning transmission electron microscopy (STEM) in conjunction with energy-dispersive X-ray spectroscopy (STEM-EDX), X-ray diffraction, and Hall effect measurements. We propose a consistent explanation to the origin of defect type, growth morphology, and transport property.Comment: 5 pages, 5 figure

Nonlinear Properties of Chalcogenide Glass Fibers

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Modified f(G) gravity models with curvature-matter coupling

A modified f(G) gravity model with coupling between matter and geometry is proposed, which is described by the product of the Lagrange density of the matter and an arbitrary function of the Gauss-Bonnet term. The field equations and the equations of motion corresponding to this model show the non-conservation of the energy-momentum tensor, the presence of an extra-force acting on test particles and the non-geodesic motion. Moreover, the energy conditions and the stability criterion at de Sitter point in the modified f(G) gravity models with curvature-matter coupling are derived, which can degenerate to the well-known energy conditions in general relativity. Furthermore, in order to get some insight on the meaning of these energy conditions, we apply them to the specific models of f(G) gravity and the corresponding constraints on the models are given. In addition, the conditions and the candidate for late-time cosmic accelerated expansion in the modified f(G) gravity are studied by means of conditions of power-law expansion and the equation of state of matter less than -1/ 3 .Comment: 13 pages, 4 figure

Inflationary Initial Conditions Consistent with Causality

The initial condition problem of inflation is examined from the perspective of both spacetime embedding and scalar field dynamics. The spacetime embedding problem is solved for arbitrary initial spatial curvature Omega, which generalizes previous works that primarily treat the flat case Omega=1. Scalar field dynamics that is consistent with the embedding constraints are examined, with the additional treatment of damping effects. The effects of inhomogeneities on the embedding problem also are considered. A category of initial conditions are identified that are not acausal and can develop into an inflationary regime.Comment: 9 pages, 3 figures. Minor changes, matches version to appear in Physical Review

Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma

We describe the clinical course of a recurrent case of congenital fibrosarcoma diagnosed in a 9-mo-old boy with a history of hemimelia. Following complete surgical resection of the primary tumor, the patient subsequently presented with bulky bilateral pulmonary metastases 6 mo following surgery. Molecular characterization of the tumor revealed the absence of the prototypical ETV6-NTRK3 translocation. However, tumor characterization incorporating cytogenetic, array comparative genomic hybridization, and RNA sequencing analyses, revealed a somatic t(2;15)(2p21;15q25) translocation resulting in the novel fusion of EML4 with NTRK3. Cloning and expression of EML4-NTRK3 in murine fibroblast NIH 3T3 cells revealed a potent tumorigenic phenotype as assessed in vitro and in vivo. These results demonstrate that multiple fusion partners targeting NTRK3 can contribute to the development of congenital fibrosarcoma

Mutations in epigenetic regulators including SETD2 are gained during relapse in pediatric acute lymphoblastic leukemia

Relapsed pediatric acute lymphoblastic leukemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signaling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance

Computing the vertices of tropical polyhedra using directed hypergraphs

We establish a characterization of the vertices of a tropical polyhedron defined as the intersection of finitely many half-spaces. We show that a point is a vertex if, and only if, a directed hypergraph, constructed from the subdifferentials of the active constraints at this point, admits a unique strongly connected component that is maximal with respect to the reachability relation (all the other strongly connected components have access to it). This property can be checked in almost linear-time. This allows us to develop a tropical analogue of the classical double description method, which computes a minimal internal representation (in terms of vertices) of a polyhedron defined externally (by half-spaces or hyperplanes). We provide theoretical worst case complexity bounds and report extensive experimental tests performed using the library TPLib, showing that this method outperforms the other existing approaches.Comment: 29 pages (A4), 10 figures, 1 table; v2: Improved algorithm in section 5 (using directed hypergraphs), detailed appendix; v3: major revision of the article (adding tropical hyperplanes, alternative method by arrangements, etc); v4: minor revisio

Vibrational Spectra of a Mechanosensitive Channel

We report the simulated vibrational spectra of a mechanosensitive membrane channel in different gating states. Our results show that while linear absorption is insensitive to structural differences, linear dichroism and sum-frequency generation spectroscopies are sensitive to the orientation of the transmembrane helices, which is changing during the opening process. Linear dichroism cannot distinguish an intermediate structure from the closed structure, but sum-frequency generation can. In addition, we find that two-dimensional infrared spectroscopy can be used to distinguish all three investigated gating states of the mechanosensitive membrane channel.