Anticancer and antibacterial potential of robust Ruthenium(II) arene complexes regulated by choice of α-diimine and halide ligands

Several complexes of general formula [Ru(halide)(η6-p-cymene)(α-diimine)]+, in the form of nitrate, triflate and hexafluorophosphate salts, including a newly synthesized iodide compound, were investigated as potential anticancer drugs and bactericides. NMR and UV–Vis studies evidenced remarkable stability of the complexes in water and cell culture medium. In general, the complexes displayed strong cytotoxicity against A2780 and A549 cancer cell lines with IC50 values in the low micromolar range, and one complex (RUCYN) emerged as the most promising one, with a significant selectivity compared to the non-cancerous HEK293 cell line. A variable affinity of the complexes for BSA and DNA binding was ascertained by spectrophotometry/fluorimetry, circular dichroism, electrophoresis and viscometry. The performance of RUCYN appears associated to enhanced cell internalization, favored by two cyclohexyl substituents, rather than to specific interaction with the evaluated biomolecules. The chloride/iodide replacement, in one case, led to increased cellular uptake and cytotoxicity at the expense of selectivity, and tuned DNA binding towards intercalation. Complexes with iodide or a valproate bioactive fragment exhibited the best antimicrobial profiles

Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained (45-92% yields) from the thermal reaction(PhCCPh exchange) of [Ru2Cp2(CO)(& mu;-CO){& mu;-& eta;(1):& eta;(3)-C(Ph)C(Ph)C(O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc),3-C6H4(Asp), 2-naphthyl; Cp = & eta;(5)-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1-3 by HBF4 afforded the corresponding & mu;-alkenyl derivatives 5-7, in 40-86% yields. All productswere characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry(1, 2, 5, 7) andsingle-crystal X-ray diffraction (5, 7)analyses were performed on representative compounds. Complexes 5-7 revealed a cytotoxic activity comparableto that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma),and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistancein A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) inducedan increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus,CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 isineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity forthis nucleic acid. Complexes 5-7 caninteract with the albumin protein with a thermodynamic signature dominatedby hydrophobic interactions. Overall, we show that organometallicspecies based on the Ru2Cp2(CO)( x ) scaffold (x = 2, 3) are activeagainst cancer cells, with different incorporated fragments influencingthe interactions with nucleic acids and the production of ROS

Dark Matter Directionality Detection performance of the Micromegas-based μ\muTPC-MIMAC detector

Directional Dark Matter Detection (DDMD) can open a new signature for Weakly Massive Interacting Particles (WIMPs) Dark Matter. The directional signature provides in addition, an unique way to overcome the neutron and neutrino backgrounds. In order to get the directional signature, the DDM detectors should be sensitive to low nuclear energy recoils in the keV range and have an angular resolution better than $20^{\circ}$. We have performed experiments with low energy ($<30\,\mathrm{keV}$) ion beam facilities to measure the angular distribution of nuclear recoil tracks in a MIMAC detector prototype. In this paper, we study angular spreads with respect to the electron drift direction ($0^{\circ}$ incident angle) of Fluorine nuclear tracks in this low energy range, and show nuclear recoil angle reconstruction produced by a monoenergetic neutron field experiment. We find that a high-gain systematic effect leads to a high angular resolution along the electron drift direction. The measured angular distribution is impacted by diffusion, and space charge or ion feedback effects, which can be corrected for by an asymmetry factor observed in the flash-ADC profile. The estimated angular resolution of the $0^{\circ}$ incident ion is better than $15^{\circ}$ at $10$ keV kinetic energy and agrees with the simulations within $20$%. The distributions from the nuclear recoils have been compared with simulated results based on a modified Garfield++ code. Our study shows that protons would be a more adapted target than heavier nuclei for DDMD of light WIMPs. We demonstrate that directional signature from the Galactic halo origin of a Dark Matter WIMP signal is experimentally achievable, with a deep understanding of the operating conditions of a low pressure detector with its diffusion mechanism.Comment: 19 pages, 12 figure

Cosmological zoo -- accelerating models with dark energy

ecent observations of type Ia supernovae indicate that the Universe is in an accelerating phase of expansion. The fundamental quest in theoretical cosmology is to identify the origin of this phenomenon. In principle there are two possibilities: 1) the presence of matter which violates the strong energy condition (a substantial form of dark energy), 2) modified Friedmann equations (Cardassian models -- a non-substantial form of dark matter). We classify all these models in terms of 2-dimensional dynamical systems of the Newtonian type. We search for generic properties of the models. It is achieved with the help of Peixoto's theorem for dynamical system on the Poincar{\'e} sphere. We find that the notion of structural stability can be useful to distinguish the generic cases of evolutional paths with acceleration. We find that, while the $\Lambda$CDM models and phantom models are typical accelerating models, the cosmological models with bouncing phase are non-generic in the space of all planar dynamical systems. We derive the universal shape of potential function which gives rise to presently accelerating models. Our results show explicitly the advantages of using a potential function (instead of the equation of state) to probe the origin of the present acceleration. We argue that simplicity and genericity are the best guide in understanding our Universe and its acceleration.Comment: RevTeX4, 23 pages, 10 figure

Testing Beam-Induced Quench Levels of LHC Superconducting Magnets

In the years 2009-2013 the Large Hadron Collider (LHC) has been operated with the top beam energies of 3.5 TeV and 4 TeV per proton (from 2012) instead of the nominal 7 TeV. The currents in the superconducting magnets were reduced accordingly. To date only seventeen beam-induced quenches have occurred; eight of them during specially designed quench tests, the others during injection. There has not been a single beam- induced quench during normal collider operation with stored beam. The conditions, however, are expected to become much more challenging after the long LHC shutdown. The magnets will be operating at near nominal currents, and in the presence of high energy and high intensity beams with a stored energy of up to 362 MJ per beam. In this paper we summarize our efforts to understand the quench levels of LHC superconducting magnets. We describe beam-loss events and dedicated experiments with beam, as well as the simulation methods used to reproduce the observable signals. The simulated energy deposition in the coils is compared to the quench levels predicted by electro-thermal models, thus allowing to validate and improve the models which are used to set beam-dump thresholds on beam-loss monitors for Run 2.Comment: 19 page

Emergency lighting cabinet for fire safety learning

The aim of this innovative educational project is to encourage students’ interest in one of the most underrated fields of fire safety: emergency lighting. So this educational project aims to combine the relationships amongst the evacuation safety theory, real manufacturers products and an specific software for its usage. In order to achieve it, a ‘technical cabinet’ has been designed and built for its use in the Laboratory of a University School. The design, content and learning system of the cabinet confirmed the validity of the initial concept during the first year of use. A protocol has also been developed for the technical cabinet, so that the teaching experience may be of use in other Schools of Architecture

AVALIAÇÃO DO ALCANCE FUNCIONAL DE INDIVÍDUOS COM LESÃO MEDULAR ESPINHAL USUÁRIOS DE CADEIRA DE RODAS

Medullar lesions consists in any type of trauma that causes motor and/or sensorial disturbs. The aim of this study was to evaluate the functional reach in paraplegic individuals, users of wheelchairs, as well as the influence of preservation of partial or total abdominal muscles. For that, 13 participants diagnosed with paraplegia, mean age 37 ± 11 years, users of a wheelchair for at least one year, were divided into two groups: G1 (levels above T8) and G2 (levels below T8). All the subjects were submitted to the Functional Reach Test, adapted to the sitting position. The statistical analysis consisted by the non-parametric test Mann Witney-U test, with a significant level of 5% (p&lt;0.05). Regarding the results, the median of the reached distance was 8.3 cm (amplitude of 6.9-49.2 cm) for G1, and 12.3 cm (amplitude of 10.8-37.9 cm) for G2. Comparing the medians between groups, there was a statistically difference (p = 0.04) regarding the values. In conclusion, the paraplegic individuals with partial or total preservation of the abdominal muscles motricity have showed great capacity of functional reach

Particle creation, renormalizability conditions and the mass-energy spectrum in gravity theories of quadratic Lagrangians

Massive scalar particle production, due to the anisotropic evolution of a five-dimensional spacetime, is considered in the context of a quadratic Lagrangian theory of gravity. Those particles, corresponding to field modes with non-vanishing momentum component along the fifth dimension, are created mostly in the neighbourhood of a singular epoch where only their high-frequency behaviour is of considerable importance. At the 1-loop approximation level, general renormalizability conditions on the physical quantities relevant to particle production are derived and discussed. Exact solutions of the resulting Klein-Gordon field equation are obtained and the mass-energy spectrum attributed to the scalar field due to the cosmological evolution is being investigated further. Finally, analytic expressions regarding the number and the energy density of the created particles at late times, are also derived and discussed.Comment: LaTeX file, 23 page