Scalar models for the unification of the dark sector

We review the difficulties of the generalized Chaplygin gas model to fit observational data, due to the tension between background and perturbative tests. We argue that such issues may be circumvented by means of a self-interacting scalar field representation of the model. However, this proposal seems to be successful only if the self-interacting scalar field has a non-canonical form. The latter can be implemented in Rastall's theory of gravity.Comment: Latex file, 8 pages, 3 figures in eps format. To appear in the proceedings of the CosmoSul conference, held in Rio de Janeiro, Brazil, 01-05 august of 201

Constitutionalising an Overlapping Consensus: The ECJ and the Emergence of a Coordinate Constitutional Order

The European Court of Justice\u27s (ECJ\u27s) jurisprudence of fundamental rights in cases such as Schmidberger and Omega extends the court\u27s jurisdiction in ways that compete with that of Member States in matters of visceral concern. And just as the Member States require a guarantee that the ECJ respect fundamental rights rooted in national tradition, so the ECJ insists that international organisations respect rights constitutive of the EU. The demand of such guarantees reproduces between the ECJ and the international order the kinds of conflicting jurisdictional claims that have shadowed the relation between the ECJ and the courts of the Member States. This article argues that the clash of jurisdiction is being resolved by the formation of a novel order of coordinate constitutionalism in which Member States, the ECJ, the European Court of Human Rights and other international tribunals or organisations agree to defer to one another\u27s decisions, provided those decisions respect mutually agreed essentials. This coordinate order extends constitutionalism beyond its home territory in the nation state through a jurisprudence of mutual monitoring and peer review that carefully builds on national constitutional traditions, but does not create a new, encompassing sovereign entity. The doctrinal instruments by which the plural constitutional orders are, in this way, profoundly linked without being integrated are variants of the familiar Solange principles of the German Constitutional Court, by which each legal order accepts the decisions of the others, even if another decision would have been more consistent with the national constitution tradition, ‘so long as’ those decisions do not systematically violate its own understanding of constitutional essentials. The article presents the coordinate constitutional order being created by this broad application of the Solange doctrine as an instance, and practical development, of what Rawls called an overlapping consensus: agreement on fundamental commitments of principle – those essentials which each order requires the others to respect – does not rest on mutual agreement on any single, comprehensive moral doctrine embracing ideas of human dignity, individuality or the like. It is precisely because the actors of each order acknowledge these persistent differences, and their continuing influence on the interpretation of shared commitments in particular conflicts, that they reserve the right to interpret essential principles, within broad and shared limits, and accord this right to others. The embrace of variants of the Solange principles by many coordinate courts, in obligating each to monitor the others\u27 respect for essentials, creates an institutional mechanism for articulating and adjusting the practical meaning of the overlapping consensus

Rastall Cosmology and the \Lambda CDM Model

Rastall's theory is based on the non-conservation of the energy-momentum tensor. We show that, in this theory, if we introduce a two-fluid model, one component representing vacuum energy whereas the other pressureless matter (e.g. baryons plus cold dark matter), the cosmological scenario is the same as for the \Lambda CDM model, both at background and linear perturbative levels, except for one aspect: now dark energy may cluster. We speculate that this can lead to a possibility of distinguishing the models at the non-linear perturbative level.Comment: 9 pages, 1 figure. Accepted for publication in Physical Review

Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells

Previous work has shown that some cancer cells are highly dependent on serine/glycine uptake for proliferation. Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serine—rather than glycine—consumption

Dark matter effects in vacuum spacetime

We analyze a toy model describing an empty spacetime in which the motion of a test mass (and the trajectories of photons) evidence the presence of a continuous and homogeneous distribution of matter; however, since the energy-momentum tensor vanishes, no real matter or energy distribution is present at all. Thus, a hypothetical observer will conclude that he is immersed in some sort of dark matter, even though he has no chance to directly detect it. This suggests yet another possibility of explaining the elusive dark matter as a purely dynamical effect due to the curvature of spacetime.Comment: 5 pages, 2 figures, expanded with comments about the exact motion and curvature invariant

Directed Evolution of a Cytochrome P450 Carbene Transferase for Selective Functionalization of Cyclic Compounds

Transfers of carbene moieties to heterocycles or cyclic alkenes to obtain C(sp^2)–H alkylation or cyclopropane products are valuable transformations for synthesis of pharmacophores and chemical building blocks. Through their readily tunable active-site geometries, hemoprotein “carbene transferases” could provide an alternative to traditional transition metal catalysts by enabling heterocycle functionalizations with high chemo-, regio-, and stereocontrol. However, carbene transferases accepting heterocyclic substrates are scarce; the few enzymes capable of heterocycle or cyclic internal alkene functionalization described to date are characterized by low turnovers or depend on artificially introduced, costly iridium–porphyrin cofactors. We addressed this challenge by evolving a cytochrome P450 for highly efficient carbene transfer to indoles, pyrroles, and cyclic alkenes. We first developed a spectrophotometric high-throughput screening assay based on 1-methylindole C3-alkylation that enabled rapid analysis of thousands of P450 variants and comprehensive directed evolution via random and targeted mutagenesis. This effort yielded a P450 variant with 11 amino acid substitutions and a large deletion of the non-catalytic P450 reductase domain, which chemoselectively C_3-alkylates indoles with up to 470 turnovers per minute and 18 000 total turnovers. We subsequently used this optimized alkylation variant for parallel evolution toward more challenging heterocycle carbene functionalizations, including C_2/C_3 regioselective pyrrole alkylation, enantioselective indole alkylation with ethyl 2-diazopropanoate, and cyclic internal alkene cyclopropanation. The resulting set of efficient biocatalysts showcases the tunability of hemoproteins for highly selective functionalization of cyclic targets and the power of directed evolution to enhance the scope of new-to-nature enzyme catalysts

The Brans-Dicke-Rastall theory

We formulate a theory combining the principles of a scalar-tensor gravity and Rastall's proposal of a violation of the usual conservation laws. We obtain a scalar-tensor theory with two parameters $\omega$ and $\lambda$, the latter quantifying the violation of the usual conservation laws. The only exact spherically symmetric solution is that of Robinson-Bertotti besides Schwarzschild solution. A PPN analysis reveals that General Relativity results are reproduced when $\lambda = 0$. The cosmological case displays a possibility of deceleration/acceleration or acceleration/deceleration transitions during the matter dominated phase depending on the values of the free parameters.Comment: 17 pages, 3 figure

Mobile intraoperative CT-assisted frameless stereotactic biopsies achieved single-millimeter trajectory accuracy for deep-seated brain lesions in a sample of 7 patients

BACKGROUND Brain biopsies are crucial diagnostic interventions, providing valuable information for treatment and prognosis, but largely depend on a high accuracy and precision. We hypothesized that through the combination of neuronavigation-based frameless stereotaxy and MRI-guided trajectory planning with intraoperative CT examination using a mobile unit, one can achieve a seamlessly integrated approach yielding optimal target accuracy. METHODS We analyzed a total of 7 stereotactic biopsy trajectories for a variety of deep-seated locations and different patient positions. After rigid head fixation, an intraoperative pre-procedural scan using a mobile CT unit was performed for automatic image fusion with the planning MRI images and a peri-procedural scan with the biopsy cannula in situ for verification of the definite target position. We then evaluated the radial trajectory error. RESULTS Intraoperative scanning, surgery, computerized merging of MRI and CT images as well as trajectory planning were feasible without difficulties and safe in all cases. We achieved a radial trajectory deviation of 0.97 ± 0.39 mm at a trajectory length of 60 ± 12.3 mm (mean ± standard deviation). Repositioning of the biopsy cannula due to inaccurate targeting was not required. CONCLUSION Intraoperative verification using a mobile CT unit in combination with frameless neuronavigation-guided stereotaxy and pre-operative MRI-based trajectory planning was feasible, safe and highly accurate. The setting enabled single-millimeter accuracy for deep-seated brain lesions and direct detection of intraoperative complications, did not depend on a dedicated operating room and was seamlessly integrated into common stereotactic procedures

Exploiting and engineering hemoproteins for abiological carbene and nitrene transfer reactions

The surge in reports of heme-dependent proteins as catalysts for abiotic, synthetically valuable carbene and nitrene transfer reactions dramatically illustrates the evolvability of the protein world and our nascent ability to exploit that for new enzyme chemistry. We highlight the latest additions to the hemoprotein-catalyzed reaction repertoire (including carbene Si–H and C–H insertions, Doyle–Kirmse reactions, aldehyde olefinations, azide-to-aldehyde conversions, and intermolecular nitrene C–H insertion) and show how different hemoprotein scaffolds offer varied reactivity and selectivity. Preparative-scale syntheses of pharmaceutically relevant compounds accomplished with these new catalysts are beginning to demonstrate their biotechnological relevance. Insights into the determinants of enzyme lifetime and product yield are providing generalizable cues for engineering heme-dependent proteins to further broaden the scope and utility of these non-natural activities