Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model

Aim: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. Materials & methods: We used 3beta-(N-[N′,N′-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). Results: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. Conclusion: These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development

Efficacy of DOPE/DC-cholesterol liposomes and GCPQ micelles as AZD6244 nanocarriers in a 3D colorectal cancer in vitro model

AIM: In this work, we use cationic organic nanocarriers as chemotherapy delivery platforms and test them in a colorectal cancer 3D in vitro model. MATERIALS & METHODS: We used 3beta-(N-[N',N'-dimethylaminoethane]carbamoyl])cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) liposomes and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) micelles, to deliver AZD6244, a MEK inhibitor, to HCT116 cells cultured as monolayers and in 3D in vitro cancer models (tumoroids). RESULTS: Nanoparticle-mediated drug delivery was superior to the free drug in monolayer experiments and despite their therapeutic effect being hindered by poor diffusion through the cancer mass, GCPQ micelles were also superior in tumoroids. CONCLUSION: These results support the role of nanoparticles in improving drug delivery and highlight the need to include 3D cancer models in early phases of drug development

Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues

We have used proteomics with cluster analysis for the classification of breast tumour tissues. In our approach, we can distinguish between normal breast, benign breast and breast cancer tissues on the basis of the protein expression profiles. We propose an objective method for the classification of breast tumour specimens

The Milky Way rotation curve in Horava - Lifshitz theory

The Horava - Lifshitz (HL) theory has recently attracted a lot of interest as a viable solution to some quantum gravity related problems and the presence of an effective cosmological constant able to drive the cosmic speed up. We show here that, in the weak field limit, the HL proposal leads to a modification of the gravitational potential because of two additive terms (scaling respectively as $r^2$ and $r^{-4}$) to the Newtonian $1/r$ potential. We then derive a general expression to compute the rotation curve of an extended system under the assumption that the mass density only depends on the cylindrical coordinates $(R, z)$ showing that the HL modification induces a dependence of the circular velocity on the mass function which is a new feature of the theory. As a first exploratory analysis, we then try fitting the Milky Way rotation curve using its visible components only in order to see whether the HL modified potential can be an alternative to the dark matter framework. This turns out not to be the case so that we argue that dark matter is still needed, but the amount of dark matter and the dark halo density profile have to be revised according to the new HL potential.Comment: 10 pages, 1 figure, accepted for publication on MNRA

Far-Ultraviolet and Far-Infrared Bivariate Luminosity Function of Galaxies: Complex Relation between Stellar and Dust Emission

Far-ultraviolet (FUV) and far-infrared (FIR) luminosity functions (LFs) of galaxies show a strong evolution from $z = 0$ to $z = 1$, but the FIR LF evolves much stronger than the FUV one. The FUV is dominantly radiated from newly formed short-lived OB stars, while the FIR is emitted by dust grains heated by the FUV radiation field. It is known that dust is always associated with star formation activity. Thus, both FUV and FIR are tightly related to the star formation in galaxies, but in a very complicated manner. In order to disentangle the relation between FUV and FIR emissions, we estimate the UV-IR bivariate LF (BLF) of galaxies with {\sl GALEX} and {\sl AKARI} All-Sky Survey datasets. Recently we invented a new mathematical method to construct the BLF with given marginals and prescribed correlation coefficient. This method makes use of a tool from mathematical statistics, so called "copula". The copula enables us to construct a bivariate distribution function from given marginal distributions with prescribed correlation and/or dependence structure. With this new formulation and FUV and FIR univariate LFs, we analyze various FUV and FIR data with {\sl GALEX}, {\sl Spitzer}, and {\sl AKARI} to estimate the UV-IR BLF. The obtained BLFs naturally explain the nonlinear complicated relation between FUV and FIR emission from star-forming galaxies. Though the faint-end of the BLF was not well constrained for high-$z$ samples, the estimated linear correlation coefficient $\rho$ was found to be very high, and is remarkably stable with redshifts (from 0.95 at $z = 0$ to 0.85 at $z = 1.0$). This implies the evolution of the UV-IR BLF is mainly due to the different evolution of the univariate LFs, and may not be controlled by the dependence structure.Comment: 10 pages, 7 figures, Earth, Planets and Space, in pres

Dust and the type II-Plateau supernova 2004dj

We present mid-infrared (MIR) spectroscopy of a Type II-plateau supernova, SN 2004dj, obtained with the Spitzer Space Telescope, spanning 106--1393 d after explosion. MIR photometry plus optical/near-IR observations are also reported. An early-time MIR excess is attributed to emission from non-silicate dust formed within a cool dense shell (CDS). Most of the CDS dust condensed between 50 d and 165 d, reaching a mass of 0.3 x 10^{-5} Msun. Throughout the observations much of the longer wavelength (>10 microns) part of the continuum is explained as an IR echo from interstellar dust. The MIR excess strengthened at later times. We show that this was due to thermal emission from warm, non-silicate dust formed in the ejecta. Using optical/near-IR line-profiles and the MIR continua, we show that the dust was distributed as a disk whose radius appeared to be slowly shrinking. The disk radius may correspond to a grain destruction zone caused by a reverse shock which also heated the dust. The dust-disk lay nearly face-on, had high opacities in the optical/near-IR regions, but remained optically thin in the MIR over much of the period studied. Assuming a uniform dust density, the ejecta dust mass by 996 d was 0.5 +/- 0.1) x 10^{-4} Msun, and exceeded 10^{-4}Msun by 1393 d. For a dust density rising toward the center the limit is higher. Nevertheless, this study suggests that the amount of freshly-synthesized dust in the SN 2004dj ejecta is consistent with that found from previous studies, and adds further weight to the claim that such events could not have been major contributors to the cosmic dust budget.Comment: ApJ in press; minor changes c.f. v

Jets and gamma-ray emission from isolated accreting black holes

The large number of isolated black holes (IBHs) in the Galaxy, estimated to be 10^8, implies a very high density of 10^-4 pc^-3 and an average distance between IBHs of 10 pc. Our study shows that the magnetic flux, accumulated on the horizon of an IBH because of accretion of interstellar matter, allows the Blandford-Znajeck mechanism to be activated. Thus, electron-positron jets can be launched. We have performed 2D numerical modelling which allowed the jet power to be estimated. Their inferred properties make such jets a feasible electron accelerator which, in molecular clouds, allows electron energy to be boosted up to 1 PeV. For the conditions expected in molecular clouds the radiative cooling time should be comparable to the escape time. Thus these sources can contribute both to the population of unidentified point-like sources and to the local cosmic ray (CR) electron spectrum. The impact of the generated electron CRs depends on the diffusion rate inside molecular clouds (MCs). If the diffusion regime in a MC is similar to Galactic diffusion, the produced electrons should rapidly escape the cloud and contribute to the Galactic CR population at very high energies >100 TeV. However, due to the modest jet luminosity (at the level of 10^35 erg s^-1) and low filling factor of MC, these sources cannot make a significant contribution to the spectrum of cosmic ray electrons at lower energies. On the other hand, if the diffusion within MCs operates at a rate close to the Bohm limit, the CR electrons escaping from the source should be confined in the cloud, significantly contributing to the local density of CRs. The IC emission of these locally-generated CRs may explain the variety of gamma ray spectra detected from nearby MCs.Comment: 6 pages, accepted by MNRA

AKARI and BLAST Observations of the Cassiopeia A Supernova Remnant and Surrounding Interstellar Medium

We use new large area far infrared maps ranging from 65 - 500 microns obtained with the AKARI and the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) missions to characterize the dust emission toward the Cassiopeia A supernova remnant (SNR). Using the AKARI high resolution data we find a new "tepid" dust grain population at a temperature of ~35K and with an estimated mass of 0.06 solar masses. This component is confined to the central area of the SNR and may represent newly-formed dust in the unshocked supernova ejecta. While the mass of tepid dust that we measure is insufficient by itself to account for the dust observed at high redshift, it does constitute an additional dust population to contribute to those previously reported. We fit our maps at 65, 90, 140, 250, 350, and 500 microns to obtain maps of the column density and temperature of "cold" dust (near 16 K) distributed throughout the region. The large column density of cold dust associated with clouds seen in molecular emission extends continuously from the surrounding interstellar medium to project on the SNR, where the foreground component of the clouds is also detectable through optical, X-ray, and molecular extinction. At the resolution available here, there is no morphological signature to isolate any cold dust associated only with the SNR from this confusing interstellar emission. Our fit also recovers the previously detected "hot" dust in the remnant, with characteristic temperature 100 K.Comment: Accepted for publication in the Astrophysical Journal. Maps and related data are available at http://blastexperiment.info

Optical and infrared observations of the Type IIP SN2002hh from day 3 to 397

We present optical and infrared (IR) observations of the type IIP SN2002hh from 3 to 397 days after explosion. The optical spectroscopic (4-397d) and photometric (3-278d) data are complemented by spectroscopic (137-381d) and photometric (137-314d) data acquired at IR wavelengths. This is the first time L-band spectra have ever been successfully obtained for a supernova at a distance beyond the Local Group. The VRI light curves in the first 40 days reveal SN2002hh to be a SN IIP (plateau) - the most common of all core-collapse supernovae. SN2002hh is one of the most highly extinguished supernovae ever investigated. To provide a good match between its early-time spectrum and a coeval spectrum of the Type IIP SN1999em, as well as maintaining consistency with KI interstellar absorption, we invoke a 2-component extinction model. One component is due to the combined effect of the interstellar medium of our Milky Way Galaxy and the SN host galaxy, while the other component is due to a "dust pocket" where the grains have a mean size smaller than in the interstellar medium. The early-time optical light curves of SNe 1999em and 2002hh are generally well-matched, as are the radioactive tails of these two SNe and SN1987A. The late-time similarity of the SN2002hh optical light curves to those of SN1987A, together with measurements of the optical/IR luminosity and [FeII] 1.257mu emission indicate that 0.07 +- 0.02 Msun of Ni 56 was ejected by SN2002hh. [... ABRIDGED...] From the [OI] 6300,6364 A doublet luminosity we infer a 16-18 Msun main-sequence progenitor star. The progenitor of SN2002hh was probably a red supergiant with a substantial, dusty wind.Comment: 32 pages, 30 figures, accepted for publication in MNRA