Bacteriophages as therapeutic and diagnostic vehicles in cancer

Evolution of nanomedicine is the re-design of synthetic and biological carriers to implement novel theranostic platforms. In recent years, bacteriophage research favors this process, which has opened up new roads in drug and gene delivery studies. By displaying antibodies, peptides, or proteins on the surface of different bacteriophages through the phage display technique, it is now possible to unravel specific molecular determinants of both cancer cells and tumor-associated microenvironmental molecules. Downstream applications are manifold, with peptides being employed most of the times to functionalize drug carriers and improve their therapeutic index. Bacteriophages themselves were proven, in this scenario, to be good carriers for imaging molecules and therapeutics as well. Moreover, manipulation of their genetic material to stably vehiculate suicide genes within cancer cells substantially changed perspectives in gene therapy. In this review, we provide examples of how amenable phages can be used as anticancer agents, especially because their systemic administration is possible. We also provide some insights into how their immunogenic profile can be modulated and exploited in immuno-oncology for vaccine production

The Core-Collapse Supernova with "Non-Uniform" Magnetic Fields

We perform two-dimensional numerical simulations on the core-collapse of a massive star with strong magnetic fields and differential rotations using a numerical code ZEUS-2D. Changing field configurations and laws of differential rotation parametrically, we compute 14 models and investigate effects of these parameters on the dynamics. In our models, we do not solve the neutrino transport and instead employ a phenomenological parametric EOS that takes into account the neutrino emissions. As a result of the calculations, we find that the field configuration plays a significant role in the dynamics of the core if the initial magnetic field is large enough. Models with initially concentrated fields produce more energetic explosions and more prolate shock waves than the uniform field. Quadrapole-like fields produce remarkably collimated and fast jet, which might be important for gamma-ray bursts(GRB). The Lorentz forces exerted in the region where the plasma-beta is less than unity are responsible for these dynamics. The pure toroidal field, on the other hand, does not lead to any explosion or matter ejection. This suggests the presupernova models of Heger et al.(2003), in which toroidal fields are predominant, is disadvantageous for the magnetorotation-induced supernova considered here. Models with initially weak magnetic fields do not lead to explosion or matter ejection, either. In these models magnetic fields play no role as they do not grow on the timescale considered in this paper so that the magnetic pressure could be comparable to the matter pressure. This is because the exponential field growth as expected in MRI is not seen in our models. The magnetic field is amplified mainly by field-compression and field-wrapping in our simulations.Comment: 24 pages, 5 figures, ApJ in press, typos correcte

Failure to downregulate the BAF53a subunit of the SWI/SNF chromatin remodeling complex contributes to the differentiation block in rhabdomyosarcoma

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Reliability of P mode event classification using contemporaneous BiSON and GOLF observations

We carried out a comparison of the signals seen in contemporaneous BiSON and GOLF data sets. Both instruments perform Doppler shift velocity measurements in integrated sunlight, although BiSON perform measurements from the two wings of potassium absorption line and GOLF from one wing of the NaD1 line. Discrepancies between the two datasets have been observed. We show,in fact, that the relative power depends on the wing in which GOLF data observes. During the blue wing period, the relative power is much higher than in BiSON datasets, while a good agreement has been observed during the red period.Comment: 7 pages, HELAS II: Helioseismology, Asteroseismology, and MHD Connections, conference proceedin

The Transcription co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation into Enterocyte vs Secretory Lineages

BACKGROUND & AIMS: Notch signaling maintains intestinal stem cells (ISCs). When ISCs exit the niche, Notch signaling among early progenitor cells at position +4/5 regulates their specification toward secretory vs enterocyte lineages (binary fate). The transcription factor ATOH1 is repressed by Notch in ISCs; its de-repression, when Notch is inactivated, drives progenitor cells to differentiate along the secretory lineage. However, it is not clear what promotes transition of ISCs to progenitors and how this fate decision is established. METHODS: We sorted cells from Lgr5-Gfp knock-in intestines from mice and characterized gene expression patterns. We analyzed Notch regulation by examining expression profiles (by quantitative reverse transcription PCR and RNAscope) of small intestinal organoids incubated with the Notch inhibitor DAPT, intestine tissues from mice given injections of the γ-secretase inhibitor dibenzazepine, and mice with intestine-specific disruption of Rbpj. We analyzed intestine tissues from mice with disruption of the RUNX1 translocation partner 1 gene (Runx1t1, also called Mtg8) or CBFA2/RUNX1 partner transcriptional co-repressor 3 (Cbfa2t3, also called Mtg16), and derived their organoids, by histology, immunohistochemistry, and RNA sequencing. We performed chromatin immunoprecipitation and sequencing analyses of intestinal crypts to identify genes regulated by MTG16. RESULTS: The transcription co-repressors MTG8 and MTG16 were highly expressed by +4/5 early progenitors, compared with other cells along crypt-villus axis. Expression of MTG8 and MTG16 were repressed by Notch signaling via ATOH1 in organoids and intestine tissues from mice. MTG8- and MTG16-knockout intestines had increased crypt hyperproliferation and expansion of ISCs, but enterocyte differentiation was impaired, based on loss of enterocyte markers and functions. Chromatin immunoprecipitation and sequencing analyses showed that MTG16 bound to promoters of genes that are specifically expressed by stem cells (such as Lgr5 and Ascl2) and repressed their transcription. MTG16 also bound to previously reported enhancer regions of genes regulated by ATOH1, including genes that encode delta-like canonical Notch ligand and other secretory-specific transcription factors. CONCLUSIONS: In intestine tissues of mice and human intestinal organoids, MTG8 and MTG16 repress transcription in the earliest progenitor cells to promote exit of ISCs from their niche (niche exit) and control the binary fate decision (secretory vs enterocyte lineage) by repressing genes regulated by ATOH1

Thermal Properties of Two-Dimensional Advection Dominated Accretion Flow

We study the thermal structure of the widely adopted two-dimensional advection dominated accretion flow (ADAF) of Narayan & Yi (1995a). The critical radius for a given mass accretion rate, outside of which the optically thin hot solutions do not exist in the equatorial plane, agrees with one-dimensional study. However, we find that, even within the critical radius, there always exists a conical region of the flow, around the pole, which cannot maintain the assumed high electron temperature, regardless of the mass accretion rate, in the absence of radiative heating. This could lead to torus-like advection inflow shape since, in general, the ions too will cool down. We also find that Compton preheating is generally important and, if the radiative efficiency, defined as the luminosity output divided by the mass accretion rate times the velocity of light squared, is above sim 4x10^-3, the polar region of the flow is preheated above the virial temperature by Compton heating and it may result in time-dependent behaviour or outflow while accretion continues in the equatorial plane. Thus, under most relevant circumstances, ADAF solutions may be expected to be accompanied by polar outflow winds. While preheating instabilities exist in ADAF, as for spherical flows, the former are to some extent protected by their characteristically higher densities and higher cooling rates, which reduce their susceptibility to Compton driven overheating.Comment: 18 pages including 4 figures. AASTEX. Submitted to Ap

Estimating the p-mode frequencies of the solar twin 18 Sco

Solar twins have been a focus of attention for more than a decade, because their structure is extremely close to that of the Sun. Today, thanks to high-precision spectrometers, it is possible to use asteroseismology to probe their interiors. Our goal is to use time series obtained from the HARPS spectrometer to extract the oscillation frequencies of 18 Sco, the brightest solar twin. We used the tools of spectral analysis to estimate these quantities. We estimate 52 frequencies using an MCMC algorithm. After examination of their probability densities and comparison with results from direct MAP optimization, we obtain a minimal set of 21 reliable modes. The identification of each pulsation mode is straightforwardly accomplished by comparing to the well-established solar pulsation modes. We also derived some basic seismic indicators using these values. These results offer a good basis to start a detailed seismic analysis of 18 Sco using stellar models.Comment: 12 pages, 6 figures, to be published in A&

Stability criterion for self-similar solutions with a scalar field and those with a stiff fluid in general relativity

A stability criterion is derived in general relativity for self-similar solutions with a scalar field and those with a stiff fluid, which is a perfect fluid with the equation of state $P=\rho$. A wide class of self-similar solutions turn out to be unstable against kink mode perturbation. According to the criterion, the Evans-Coleman stiff-fluid solution is unstable and cannot be a critical solution for the spherical collapse of a stiff fluid if we allow sufficiently small discontinuity in the density gradient field in the initial data sets. The self-similar scalar-field solution, which was recently found numerically by Brady {\it et al.} (2002 {\it Class. Quantum. Grav.} {\bf 19} 6359), is also unstable. Both the flat Friedmann universe with a scalar field and that with a stiff fluid suffer from kink instability at the particle horizon scale.Comment: 15 pages, accepted for publication in Classical and Quantum Gravity, typos correcte

A complete classification of spherically symmetric perfect fluid similarity solutions

We classify all spherically symmetric perfect fluid solutions of Einstein's equations with equation of state p/mu=a which are self-similar in the sense that all dimensionless variables depend only upon z=r/t. For a given value of a, such solutions are described by two parameters and they can be classified in terms of their behaviour at large and small distances from the origin; this usually corresponds to large and small values of z but (due to a coordinate anomaly) it may also correspond to finite z. We base our analysis on the demonstration that all similarity solutions must be asymptotic to solutions which depend on either powers of z or powers of lnz. We show that there are only three similarity solutions which have an exact power-law dependence on z: the flat Friedmann solution, a static solution and a Kantowski-Sachs solution (although the latter is probably only physical for a1/5, there are also two families of solutions which are asymptotically (but not exactly) Minkowski: the first is asymptotically Minkowski as z tends to infinity and is described by one parameter; the second is asymptotically Minkowski at a finite value of z and is described by two parameters. A complete analysis of the dust solutions is given, since these can be written down explicitly and elucidate the link between the z>0 and z<0 solutions. Solutions with pressure are then discussed in detail; these share many of the characteristics of the dust solutions but they also exhibit new features.Comment: 63 pages. To appear in Physical Review

Ejection of the inner accretion disk in GRS 1915+105: the magnetic rubber-band effect

We examine theoretically the behaviour of the inner accretion disk in GRS 1915+105 when soft X-ray dips are present in the X-ray light curve. We assume the presence of a radial shock in the accretion disk, as in some of the Two Component Advective Flow (TCAF) solutions. We discuss the behaviour of the flux tubes inside a TCAF (which we name Magnetized TCAF or MTCAF model for brevity) and compare various competing forces on the flux tubes. In this MTCAF model, we find that the magnetic tension is the strongest force in a hot plasma of temperature \gsim 10^{10}K and as a result, magnetic flux tubes entering in this region collapse catastrophically, thereby occasionally evacuating the inner disk. We postulate that this magnetic `rubber-band' effect induced evacuated disk matter produces the blobby components of outflows and IR/radio jets. We derive the size of the post-shock region by equating the time scale of the Quasi-Periodic Oscillations to the infall time of accreting matter in the post-shock region and found the shock location to be $\sim 45-66 r_g$. We calculate the transition radius $r_{tr}$, where the Keplerian disk deviates into a sub-Keplerian flow, to be $\sim 320r_g$. Based on the derived X-ray spectral parameters, we calculate the mass of this region to be $\sim10^{18}$g. We conclude that during the X-ray dips the matter in the post-shock region, which manifests itself as the thermal-Compton component in the X-ray spectrum, is ejected, along with some sub-Keplerian matter in the pre-shock region.Comment: 7 Latex pages and one figur