The development of RAPTA compounds for the treatment of tumors

© 2015 Elsevier B.V. Ruthenium(II)-arene RAPTA-type compounds have been extensively explored for their medicinal properties. Herein a comprehensive review of this class of compounds is provided. A discussion of the basic RAPTA structure is given together with the ways it has been modified to elucidate the key role of each part and to afford targeted derivatives. The various mechanistic studies conducted on RAPTA compounds are described and these are linked to the observed macroscopic biological properties. Ultimately, the review shows that certain RAPTA compounds display quite unique properties that point towards a clinical investigation

Random template placement and prior information

In signal detection problems, one is usually faced with the task of searching a parameter space for peaks in the likelihood function which indicate the presence of a signal. Random searches have proven to be very efficient as well as easy to implement, compared e.g. to searches along regular grids in parameter space. Knowledge of the parameterised shape of the signal searched for adds structure to the parameter space, i.e., there are usually regions requiring to be densely searched while in other regions a coarser search is sufficient. On the other hand, prior information identifies the regions in which a search will actually be promising or may likely be in vain. Defining specific figures of merit allows one to combine both template metric and prior distribution and devise optimal sampling schemes over the parameter space. We show an example related to the gravitational wave signal from a binary inspiral event. Here the template metric and prior information are particularly contradictory, since signals from low-mass systems tolerate the least mismatch in parameter space while high-mass systems are far more likely, as they imply a greater signal-to-noise ratio (SNR) and hence are detectable to greater distances. The derived sampling strategy is implemented in a Markov chain Monte Carlo (MCMC) algorithm where it improves convergence.Comment: Proceedings of the 8th Edoardo Amaldi Conference on Gravitational Waves. 7 pages, 4 figure

Finite-Range Gravity and Its Role in Gravitational Waves, Black Holes and Cosmology

Theoretical considerations of fundamental physics, as well as certain cosmological observations, persistently point out to permissibility, and maybe necessity, of macroscopic modifications of the Einstein general relativity. The field-theoretical formulation of general relativity helped us to identify the phenomenological seeds of such modifications. They take place in the form of very specific mass-terms, which appear in addition to the field-theoretical analog of the usual Hilbert-Einstein Lagrangian. We interpret the added terms as masses of the spin-2 and spin-0 gravitons. The arising finite-range gravity is a fully consistent theory, which smoothly approaches general relativity in the massless limit, that is, when both masses tend to zero and the range of gravity tends to infinity. We show that all local weak-field predictions of the theory are in perfect agreement with the available experimental data. However, some other conclusions of the non-linear massive theory are in a striking contrast with those of general relativity. We show in detail how the arbitrarily small mass-terms eliminate the black hole event horizon and replace a permanent power-law expansion of a homogeneous isotropic universe with an oscillatory behaviour. One variant of the theory allows the cosmological scale factor to exhibit an `accelerated expansion'instead of slowing down to a regular maximum of expansion. We show in detail why the traditional, Fierz-Pauli, massive gravity is in conflict not only with the static-field experiments but also with the available indirect gravitational-wave observations. At the same time, we demonstrate the incorrectness of the widely held belief that the non-Fierz-Pauli theories possess `negative energies' and `instabilities'.Comment: 56 pages including 11 figures; significant modifications; in particular, we demonstrate the incorrectness of the widely held belief that the non-Fierz-Pauli theories should suffer from negative energies and instabilities; to appear in Int. J. Mod. Phys.

LISA as a dark energy probe

Recently it was shown that the inclusion of higher signal harmonics in the inspiral signals of binary supermassive black holes (SMBH) leads to dramatic improvements in parameter estimation with the Laser Interferometer Space Antenna (LISA). In particular, the angular resolution becomes good enough to identify the host galaxy or galaxy cluster, in which case the redshift can be determined by electromagnetic means. The gravitational wave signal also provides the luminosity distance with high accuracy, and the relationship between this and the redshift depends sensitively on the cosmological parameters, such as the equation-of-state parameter $w=p_{\rm DE}/\rho_{\rm DE}$ of dark energy. With a single binary SMBH event at $z < 1$ having appropriate masses and orientation, one would be able to constrain $w$ to within a few percent. We show that, if the measured sky location is folded into the error analysis, the uncertainty on $w$ goes down by an additional factor of 2-3, leaving weak lensing as the only limiting factor in using LISA as a dark energy probe.Comment: 11pages, 1 Table, minor changes in text, accepted for publication in Classical and Quantum Gravity (special issue for proceedings of 7th LISA symposium

Rational mucolytic therapy with ambroxol: controversial and indisputable. A review

Many years of experience in the use of ambroxol is based on its ability to regulate the basic mechanisms of physiological production and transport of bronchial mucus. The main indication for ambroxol is the mucolytic therapy of acute and chronic bronchopulmonary diseases associated with hypersecretion and impaired mucus transport. Ambroxol has a number of the following properties: high secretolytic activity (promotes mucus clearance, facilitates expectoration of sputum, reduces productive cough); anti-inflammatory and antioxidant activity; local analgesic (anesthetic) effect through the blockade of sodium channels of cell membranes. The effect of anesthesia of the mucous membranes is attributed to the new pharmacological action of ambroxol, useful in the treatment of acute respiratory tract infections. The efficacy and safety of ambroxol in clinical practice has been confirmed by half a century of experience in its administration. The purpose of this publication was an up-to-date assessment of the controversial and indisputable chemical, pharmacological, clinical data on the properties of ambroxol in the concept of modern recovery mucolytic therapy that can improve the therapy and prognosis of patients with tracheobronchial secretion hypersecretion, impaired mucociliary clearance and unproductive cough

Binary black hole spectroscopy

We study parameter estimation with post-Newtonian (PN) gravitational waveforms for the quasi-circular, adiabatic inspiral of spinning binary compact objects. The performance of amplitude-corrected waveforms is compared with that of the more commonly used restricted waveforms, in Advanced LIGO and EGO. With restricted waveforms, the properties of the source can only be extracted from the phasing. For amplitude-corrected waveforms, the spectrum encodes a wealth of additional information, which leads to dramatic improvements in parameter estimation. At distances of $\sim 100$ Mpc, the full PN waveforms allow for high-accuracy parameter extraction for total mass up to several hundred solar masses, while with the restricted ones the errors are steep functions of mass, and accurate parameter estimation is only possible for relatively light stellar mass binaries. At the low-mass end, the inclusion of amplitude corrections reduces the error on the time of coalescence by an order of magnitude in Advanced LIGO and a factor of 5 in EGO compared to the restricted waveforms; at higher masses these differences are much larger. The individual component masses, which are very poorly determined with restricted waveforms, become measurable with high accuracy if amplitude-corrected waveforms are used, with errors as low as a few percent in Advanced LIGO and a few tenths of a percent in EGO. The usual spin-orbit parameter $\beta$ is also poorly determined with restricted waveforms (except for low-mass systems in EGO), but the full waveforms give errors that are small compared to the largest possible value consistent with the Kerr bound. This suggests a way of finding out if one or both of the component objects violate this bound. We also briefly discuss the effect of amplitude corrections on parameter estimation in Initial LIGO.Comment: 28 pages, many figures. Final version accepted by CQG. More in-depth treatment of component mass errors and detectability of Kerr bound violations; improved presentatio

Testing Alternative Theories of Gravity using LISA

We investigate the possible bounds which could be placed on alternative theories of gravity using gravitational wave detection from inspiralling compact binaries with the proposed LISA space interferometer. Specifically, we estimate lower bounds on the coupling parameter \omega of scalar-tensor theories of the Brans-Dicke type and on the Compton wavelength of the graviton \lambda_g in hypothetical massive graviton theories. In these theories, modifications of the gravitational radiation damping formulae or of the propagation of the waves translate into a change in the phase evolution of the observed gravitational waveform. We obtain the bounds through the technique of matched filtering, employing the LISA Sensitivity Curve Generator (SCG), available online. For a neutron star inspiralling into a 10^3 M_sun black hole in the Virgo Cluster, in a two-year integration, we find a lower bound \omega > 3 * 10^5. For lower-mass black holes, the bound could be as large as 2 * 10^6. The bound is independent of LISA arm length, but is inversely proportional to the LISA position noise error. Lower bounds on the graviton Compton wavelength ranging from 10^15 km to 5 * 10^16 km can be obtained from one-year observations of massive binary black hole inspirals at cosmological distances (3 Gpc), for masses ranging from 10^4 to 10^7 M_sun. For the highest-mass systems (10^7 M_sun), the bound is proportional to (LISA arm length)^{1/2} and to (LISA acceleration noise)^{-1/2}. For the others, the bound is independent of these parameters because of the dominance of white-dwarf confusion noise in the relevant part of the frequency spectrum. These bounds improve and extend earlier work which used analytic formulae for the noise curves.Comment: 16 pages, 9 figures, submitted to Classical & Quantum Gravit

Molecular-genetic mechanisms underlying fruit and seed coloration in plants

Diverse patterns of plant fruit and seed coloration are determined by the presence of two main types of pigment, carotenoids (red, orange and yellow color) and anthocyanins (purple, blue, red). Thеy belong to two groups of secondary metabolites, isoprenoids and flavonoids. Interest towards the genetic mechanisms that control coloration in plants has recently increased due to the antioxidant and antimicrobial properties of some pigments and their colorless precursors consumed with plant-derived food. The genes encoding enzymes involved in step-bystep conversion of initial organic molecules to final pigmented compounds are referred to as structural genes, while regulatory genes are responsible for activation of the expression of structural genes and control the synthesis of pigments at certain times and in proper tissue. The data in plant genetics accumulated to date show that the inter- and intraspecies phenotypic diversity in coloration is mainly related with regulatory genes. Previously developed rich gene collections and precise genetic models for coloration traits in dicots and monocots as well as the rapid development of molecular genetic methods for studying plants allowed for studying genetic regulation of pigment synthesis at a molecular level. The peculiarities of the regulation of carotenoid biosynthesis are exemplified with Solanaceae fruits. The genetic mechanisms underlying the synthesis of various flavonoid pigments are exemplified with a study of seed color in Poaceae plants. In summary, prospects for the practical use of regulatory genes that control pigment synthesis are discussed and examples of their practical use in vegetable and cereal crop breeding are given

Mapping spacetimes with LISA: inspiral of a test-body in a `quasi-Kerr' field

The future LISA detector will constitute the prime instrument for high-precision gravitational wave observations.LISA is expected to provide information for the properties of spacetime in the vicinity of massive black holes which reside in galactic nuclei.Such black holes can capture stellar-mass compact objects, which afterwards slowly inspiral,radiating gravitational waves.The body's orbital motion and the associated waveform carry information about the spacetime metric of the massive black hole,and it is possible to extract this information and experimentally identify (or not!) a Kerr black hole.In this paper we lay the foundations for a practical `spacetime-mapping' framework. Our work is based on the assumption that the massive body is not necessarily a Kerr black hole, and that the vacuum exterior spacetime is stationary axisymmetric,described by a metric which deviates slightly from the Kerr metric. We first provide a simple recipe for building such a `quasi-Kerr' metric by adding to the Kerr metric the deviation in the value of the quadrupole moment. We then study geodesic motion in this metric,focusing on equatorial orbits. We proceed by computing `kludge' waveforms which we compare with their Kerr counterparts. We find that a modest deviation from the Kerr metric is sufficient for producing a significant mismatch between the waveforms, provided we fix the orbital parameters. This result suggests that an attempt to use Kerr waveform templates for studying EMRIs around a non-Kerr object might result in serious loss of signal-to-noise ratio and total number of detected events. The waveform comparisons also unveil a `confusion' problem, that is the possibility of matching a true non-Kerr waveform with a Kerr template of different orbital parameters.Comment: 19 pages, 6 figure

Universally Coupled Massive Gravity

We derive Einstein's equations from a linear theory in flat space-time using free-field gauge invariance and universal coupling. The gravitational potential can be either covariant or contravariant and of almost any density weight. We adapt these results to yield universally coupled massive variants of Einstein's equations, yielding two one-parameter families of distinct theories with spin 2 and spin 0. The Freund-Maheshwari-Schonberg theory is therefore not the unique universally coupled massive generalization of Einstein's theory, although it is privileged in some respects. The theories we derive are a subset of those found by Ogievetsky and Polubarinov by other means. The question of positive energy, which continues to be discussed, might be addressed numerically in spherical symmetry. We briefly comment on the issue of causality with two observable metrics and the need for gauge freedom and address some criticisms by Padmanabhan of field derivations of Einstein-like equations along the way.Comment: Introduction notes resemblance between Einstein's discovery process and later field/spin 2 project; matches journal versio