Equilibrium hydrostatic equation and Newtonian limit of the singular f(R) gravity

We derive the equilibrium hydrostatic equation of a spherical star for any gravitational Lagrangian density of the form $L=\sqrt{-g}f(R)$. The Palatini variational principle for the Helmholtz Lagrangian in the Einstein gauge is used to obtain the field equations in this gauge. The equilibrium hydrostatic equation is obtained and is used to study the Newtonian limit for $f(R)=R-\frac{a^{2}}{3R}$. The same procedure is carried out for the more generally case $f(R)=R-\frac{1}{n+2}\frac{a^{n+1}}{R^{n}}$ giving a good Newtonian limit.Comment: Revised version, to appear in Classical and Quantum Gravity

Role of Src homology domain binding in signaling complexes assembled by the murid γ-herpesvirus M2 protein

γ-Herpesviruses express proteins that modulate B lymphocyte signaling to achieve persistent latent infections. One such protein is the M2 latency-associated protein encoded by the murid herpesvirus-4. M2 has two closely spaced tyrosine residues, Tyr120 and Tyr129, which are phosphorylated by Src family tyrosine kinases. Here we used mass spectrometry to identify the binding partners of tyrosine-phosphorylated M2. Each M2 phosphomotif is shown to bind directly and selectively to SH2-containing signaling molecules. Specifically, Src family kinases, NCK1 and Vav1, bound to the Tyr(P)120 site, PLCγ2 and the SHP2 phosphatase bound to the Tyr(P)129 motif, and the p85α subunit of PI3K associated with either motif. Consistent with these data, we show that M2 coordinates the formation of multiprotein complexes with these proteins. The effect of those interactions is functionally bivalent, because it can result in either the phosphorylation of a subset of binding proteins (Vav1 and PLCγ2) or in the inactivation of downstream targets (AKT). Finally, we show that translocation to the plasma membrane and subsequent M2 tyrosine phosphorylation relies on the integrity of a C-terminal proline-rich SH3 binding region of M2 and its interaction with Src family kinases. Unlike other γ-herpesviruses, that encode transmembrane proteins that mimic the activation of ITAMs, murid herpesvirus-4 perturbs B cell signaling using a cytoplasmic/membrane shuttling factor that nucleates the assembly of signaling complexes using a bilayered mechanism of phosphotyrosine and proline-rich anchoring motifs.This work was supported by Portuguese Fundação para a Ciência e Tecnologia (FCT) Grant PTDC/SAU-MII/099314/2008 (to J. P. S.) and Spanish Association Against Cancer and Spanish Ministry of Economy and Competitiveness Grants SAF2009-07172 and RD06/0020/0001, respectively (to X. R. B.). Spanish funding is co-sponsored by the European FEDER program. The SPR equipment at the Instituto de Tecnologia Química e Biológica was acquired with FCT Grant PNRC/692/BIO/2264/2005.Peer Reviewe

Developing a Business Application with BPM and MDE

In this paper we have designed an architecture for the generation of a business application, that allows to business users to adapt their processes to the constant change. At the moment all the architectures based to a great extent on SOA allow to modify the processes in a short period of time, but we go beyond and give the possibility to the business user of modifying their processes. To design this architecture, we rely on the fundamental use of two technologies: BPM (Business Process Modeling) and MDE (Model Driven Engineering). Inside these technologies we focus on the creation of a business process notation extended from BPMN that is agile, easy to learn and design, and capable to provide semantic information about the process. Therefore this notation allows business process to modify their processes to achieve the proposed goal

Vav3 Is Involved in GABAergic Axon Guidance Events Important for the Proper Function of Brainstem Neurons Controlling Cardiovascular, Respiratory, and Renal Parameters

Vav3 is a phosphorylation GDP/GTP exchange factor for Rho/Rac GTPases. Recently, it has been described that Vav3 knockout mice develop hypertension and sympathoexcitation. In this work, we report the neurological cause of this phenotype

The Gammaherpesvirus m2 Protein Manipulates the Fyn/Vav Pathway through a Multidocking Mechanism of Assembly

To establish latent infections in B-cells, gammaherpesviruses express proteins in the infected B-cells of the host that spuriously activate signalling pathways located downstream of the B-cell receptor. One such protein is M2, a murine gammaherpesvirus 68-encoded molecule that activates the Vav1/Rac1 pathway via the formation of trimolecular complexes with Scr family members. Previous reports have shown that the formation of this heteromolecular complex involves interactions between a proline rich region of M2 and the Vav1 and Fyn SH3 domains. Here, we show that the optimal association of these proteins requires a second structural motif encompassing two tyrosine residues (Tyr120 and 129). These residues are inducibly phosphorylated by Fyn in non-hematopoietic cells and constitutively phosphorylated in B-cells. We also demonstrate that the phosphorylation of Tyr120 creates specific docking sites for the SH2 domains of both Vav1 and Fyn, a condition sine qua non for the optimal association of these two signalling proteins in vivo. Interestingly, signaling experiments indicate that the expression of M2 in B-cells promotes the tyrosine phosphorylation of Vav1 and additional signaling proteins, a biological process that requires the integrity of both the M2 phosphotyrosine and proline rich region motifs. By infecting mice with viruses mutated in the m2 locus, we show that the integrity of each of these two M2 docking motifs is essential for the early steps of murine gammaherpesvirus-68 latency. Taken together, these results indicate that the M2 phosphotyrosine motif and the previously described M2 proline rich region work in a concerted manner to manipulate the signaling machinery of the host B-cell

Spherical symmetry in f(R)f(R)-gravity

Spherical symmetry in $f(R)$ gravity is discussed in details considering also the relations with the weak field limit. Exact solutions are obtained for constant Ricci curvature scalar and for Ricci scalar depending on the radial coordinate. In particular, we discuss how to obtain results which can be consistently compared with General Relativity giving the well known post-Newtonian and post-Minkowskian limits. Furthermore, we implement a perturbation approach to obtain solutions up to the first order starting from spherically symmetric backgrounds. Exact solutions are given for several classes of $f(R)$ theories in both $R =$ constant and $R = R(r)$.Comment: 13 page

Human Vav1 Expression in Hematopoietic and Cancer Cell Lines Is Regulated by c-Myb and by CpG Methylation

Vav1 is a signal transducer protein that functions as a guanine nucleotide exchange factor for the Rho/Rac GTPases in the hematopoietic system where it is exclusively expressed. Recently, Vav1 was shown to be involved in several human malignancies including neuroblastoma, lung cancer, and pancreatic ductal adenocarcinoma (PDA). Although some factors that affect vav1 expression are known, neither the physiological nor pathological regulation of vav1 expression is completely understood. We demonstrate herein that mutations in putative transcription factor binding sites at the vav1 promoter affect its transcription in cells of different histological origin. Among these sites is a consensus site for c-Myb, a hematopoietic-specific transcription factor that is also found in Vav1-expressing lung cancer cell lines. Depletion of c-Myb using siRNA led to a dramatic reduction in vav1 expression in these cells. Consistent with this, co-transfection of c-Myb activated transcription of a vav1 promoter-luciferase reporter gene construct in lung cancer cells devoid of Vav1 expression. Together, these results indicate that c-Myb is involved in vav1 expression in lung cancer cells. We also explored the methylation status of the vav1 promoter. Bisulfite sequencing revealed that the vav1 promoter was completely unmethylated in human lymphocytes, but methylated to various degrees in tissues that do not normally express vav1. The vav1 promoter does not contain CpG islands in proximity to the transcription start site; however, we demonstrated that methylation of a CpG dinucleotide at a consensus Sp1 binding site in the vav1 promoter interferes with protein binding in vitro. Our data identify two regulatory mechanisms for vav1 expression: binding of c-Myb and CpG methylation of 5′ regulatory sequences. Mutation of other putative transcription factor binding sites suggests that additional factors regulate vav1 expression as well

Counteranion-Dependent Reaction Pathways in the Protonation of Cationic Ruthenium−Vinylidene Complexes

The tetraphenylborate salts of the cationic vinylidene complexes [Cp*Ru=C=CHR(iPr2PNHPy)]+ (R = p-C6H4CF3 (1a-BPh4), Ph (1b-BPh4), p-C6H4CH3 (1c- BPh4), p-C6H4Br (1d-BPh4), tBu (1e-BPh4), H (1f-BPh4)) have been protonated using an excess of HBF4·OEt2 in CD2Cl2, furnishing the dicationic carbyne complexes [Cp*Ru≡CCH2R(iPr2PNHPy)]2+ (R = p-C6H4CF3 (2a), Ph (2b), p-C6H4CH3 (2c), p-C6H4Br (2d), tBu (2e), H (2f)), which were characterized in solution at low temperature by NMR spectroscopy. The corresponding reaction of the chloride salts 1a-Cl, 1b-Cl, 1c-Cl, and 1d-Cl followed a different pathway, instead affording the novel alkene complexes [Cp*RuCl(κ1(N),η2(C,C)-C5H4N-NHPiPr2CH=CHR)][BF4] (3a−d). In these species, the entering proton is located at the α- carbon atom of the former vinylidene ligand, which also forms a P−C bond with the phosphorus atom of the iPr2PNHPy ligand. To shed light on the reaction mechanism, DFT calculations have been performed by considering several protonation sites. The computational results suggest metal protonation followed by insertion. The coordination of chloride to ruthenium leads to alkenyl species which can undergo a P−C coupling to yield the corresponding alkene complexes. The noncoordinating nature of [BPh4]− does not allow the stabilization of the unsaturated species coming from the insertion step, thus preventing this alternative pathway

Compactifying the state space for alternative theories of gravity

In this paper we address important issues surrounding the choice of variables when performing a dynamical systems analysis of alternative theories of gravity. We discuss the advantages and disadvantages of compactifying the state space, and illustrate this using two examples. We first show how to define a compact state space for the class of LRS Bianchi type I models in $R^n$-gravity and compare to a non--compact expansion--normalised approach. In the second example we consider the flat Friedmann matter subspace of the previous example, and compare the compact analysis to studies where non-compact non--expansion--normalised variables were used. In both examples we comment on the existence of bouncing or recollapsing orbits as well as the existence of static models.Comment: 18 pages, revised to match published versio

Developing a Business Application with BPM and MDE

In this paper we have designed an architecture for the generation of a business application, that allows to business users to adapt their processes to the constant change. At the moment all the architectures based to a great extent on SOA allow to modify the processes in a short period of time, but we go beyond and give the possibility to the business user of modifying their processes. To design this architecture, we rely on the fundamental use of two technologies: BPM (Business Process Modeling) and MDE (Model Driven Engineering). Inside these technologies we focus on the creation of a business process notation extended from BPMN that is agile, easy to learn and design, and capable to provide semantic information about the process. Therefore this notation allows business process to modify their processes to achieve the proposed goal