Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

A model of population dynamics of TB in a prison system and application to South Africa

BACKGROUND: Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. RESULTS: We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the prison population can be either by death or by being released from prison, as compared to a general population in which removal is only by death. We describe conditions, including non-inflow of infectives into the prison, which will ensure that TB can be eradicated from the prison population. The model is calibrated for the South African prison system, by using data in existing literature. The model can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Illustrative simulations in this regard are presented. The model can be used for other prison populations too, if data is available to calculate the model parameters. CONCLUSIONS: Various simulations generated with our model serve to illustrate how it can be utilized in making future projections of the levels of prevalence of TB, and to quantify the effect of interventions such as screening, treatment or reduction of transmission parameter values through improved living conditions for inmates. This makes it particularly useful as there are various targets set by the World Health Organization and by governments, for reduction of TB prevalence and ultimately its eradication. Towards eradication of TB from a prison system, the theorem on global stability of the disease-free state is a useful indicator

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

A Monofunctional Platinum Complex Coordinated to a Rhodium Metalloinsertor Selectively Binds Mismatched DNA in the Minor Groove

We report the synthesis and characterization of a bimetallic complex derived from a new family of potent and selective metalloinsertors containing an unusual Rh–O axial coordination. This complex incorporates a monofunctional platinum center containing only one labile site for coordination to DNA, rather than two, and coordinates DNA nonclassically through adduct formation in the minor groove. This conjugate displays bifunctional, interdependent binding of mismatched DNA via metalloinsertion at a mismatch as well as covalent platinum binding. DNA sequencing experiments revealed that the preferred site of platinum coordination is not the traditional N7-guanine site in the major groove, but rather N3-adenine in the minor groove. The complex also displays enhanced cytotoxicity in mismatch repair-deficient and mismatch repair-proficient human colorectal carcinoma cell lines compared to the chemotherapeutic cisplatin, and it triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors

An instrumented baffle for the Advanced Virgo Input Mode Cleaner End Mirror

A novel instrumented baffle surrounding the suspended end mirror in the input mode cleaner cavity of the Virgo interferometer was installed in spring 2021. Since then, the device has been regularly operated in the experiment and the obtained results indicate a good agreement with simulations of the stray light inside the optical cavity. The baffle will operate in the upcoming O4 observation run, serving as a demonstrator of the technology designed to instrument the baffles in front of the main mirrors in time for O5. In this paper we present a detailed description of the baffle design, including mechanics, front-end electronics, data acquisition, as well as optical and vacuum tests, calibration and installation procedures, and performance results.Comment: 12 pages, 21 figures, 3 tables, to be submitted to PR

MUM ENHANCERS are important for seed coat mucilage production and mucilage secretory cell differentiation in Arabidopsis thaliana

Pollination triggers not only embryo development but also the differentiation of the ovule integuments to form a specialized seed coat. The mucilage secretory cells of the Arabidopsis thaliana seed coat undergo a complex differentiation process in which cell growth is followed by the synthesis and secretion of pectinaceous mucilage. A number of genes have been identified affecting mucilage secretory cell differentiation, including MUCILAGE-MODIFIED4 (MUM4). mum4 mutants produce a reduced amount of mucilage and cloning of MUM4 revealed that it encodes a UDP-L-rhamnose synthase that is developmentally up-regulated to provide rhamnose for mucilage pectin synthesis. To identify additional genes acting in mucilage synthesis and secretion, a screen for enhancers of the mum4 phenotype was performed. Eight mum enhancers (men) have been identified, two of which result from defects in known mucilage secretory cell genes (MUM2 and MYB61). Our results show that, in a mum4 background, mutations in MEN1, MEN4, and MEN5 lead to further reductions in mucilage compared to mum4 single mutants, suggesting that they are involved in mucilage synthesis or secretion. Conversely, mutations in MEN2 and MEN6 appear to affect mucilage release rather than quantity. With the exception of men4, whose single mutant exhibits reduced mucilage, none of these genes have a single mutant phenotype, suggesting that they would not have been identified outside the compromised mum4 background

The Advanced Virgo+ status

The gravitational wave detector Advanced Virgo+ is currently in the commissioning phase in view of the fourth Observing Run (O4). The major upgrades with respect to the Advanced Virgo configuration are the implementation of an additional recycling cavity, the Signal Recycling cavity (SRC), at the output of the interferometer to broaden the sensitivity band and the Frequency Dependent Squeezing (FDS) to reduce quantum noise at all frequencies. The main difference of the Advanced Virgo + detector with respect to the LIGO detectors is the presence of marginally stable recycling cavities, with respect to the stable recycling cavities present in the LIGO detectors, which increases the difficulties in controlling the interferometer in presence of defects (both thermal and cold defects). This work will focus on the interferometer commissioning, highlighting the control challenges to maintain the detector in the working point which maximizes the sensitivity and the duty cycle for scientific data taking

Advanced Virgo Plus: Future Perspectives

While completing the commissioning phase to prepare the Virgo interferometer for the next joint Observation Run (O4), the Virgo collaboration is also finalizing the design of the next upgrades to the detector to be employed in the following Observation Run (O5). The major upgrade will concern decreasing the thermal noise limit, which will imply using very large test masses and increased laser beam size. But this will not be the only upgrade to be implemented in the break between the O4 and O5 observation runs to increase the Virgo detector strain sensitivity. The paper will cover the challenges linked to this upgrade and implications on the detector's reach and observational potential, reflecting the talk given at 12th Cosmic Ray International Seminar - CRIS 2022 held in September 2022 in Napoli

A Standard Siren Measurement of the Hubble Constant from GW170817 without the Electromagnetic Counterpart

We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago

Calibration of advanced Virgo and reconstruction of the detector strain h( t) during the observing run O3

The three advanced Virgo and LIGO gravitational wave detectors participated to the third observing run (O3) between 1 April 2019 15:00 UTC and 27 March 2020 17:00 UTC, leading to several gravitational wave detections per month. This paper describes the advanced Virgo detector calibration and the reconstruction of the detector strain h(t) during O3, as well as the estimation of the associated uncertainties. For the first time, the photon calibration technique as been used as reference for Virgo calibration, which allowed to cross-calibrate the strain amplitude of the Virgo and LIGO detectors. The previous reference, so-called free swinging Michelson technique, has still been used but as an independent cross-check. h(t) reconstruction and noise subtraction were processed online, with good enough quality to prevent the need for offline reprocessing, except for the two last weeks of September 2019. The uncertainties for the reconstructed h(t) strain, estimated in this paper in a 20-2000 Hz frequency band, are frequency independent: 5% in amplitude, 35 mrad in phase and 10 μs in timing, with the exception of larger uncertainties around 50 Hz