Identification of three gene candidates for multicellular resistance in colon carcinoma

Solid tumours display elevated resistance to chemo- and radiotherapies compared to individual tumour derived cells. This so-called multicellular resistance (MCR) phenomenon can only be partly explained by reduced diffusion and altered cell cycle status; even fast growing cells on the surface of solid tumours display MCR. Multicellular spheroids (MCS) recapture this phenomenon ex vivo and here we compare gene expression in exponentially growing MCS with gene expression in monolayer culture. Using an 18,664 gene microarray, we identified 42 differentially expressed genes and three of these genes can be linked to potential mechanisms of MCR. A group of interferon response genes were also up-regulated in MCS, as were a number of genes that that are indicative of greater differentiation in three-dimensional cultures.

Emulsion strategies in the microencapsulation of cells: Pathways to thin coherent membranes

Microencapsulation of cell spheroids in an immunoselective, highly biocompatible, biomembrane offers a way to create viable implantation options in the treatment of insulin-dependent diabetes mellitus (IDDM). Traditionally the encapsulation process has been achieved through the injection/extrusion of alginate/cell mixtures into a calcium chloride solution to produce calcium alginate capsules around the cells. A novel alternative is explored here through a procedure using an emulsion process to produce thin adherent calcium alginate membranes around cell spheroids. In this study, a thorough investigation has been used to establish the emulsion process parameters that are critical to the formation of a coherent alginate coat both on a model spheroid system and subsequently on cell spheroids. Optical and fluorescence microscopy are used to assess the morphology and coherence of the calcium alginate/ poly-L-ornithine/alginate (APA) capsules produced. (c) 2005 Wiley Periodicals, Inc.

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7WT cells or a drug-resistant, P-gp-expressing derivative MCF7Adr. Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TSWT, whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TSAdr resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TSWT. The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds.

Satellites around massive galaxies since z∼ 2

The accretion of minor satellites has been postulated as the most likely mechanism to explain the significant size evolution of massive galaxies over cosmic time. Using a sample of 629 massive (M_star~ 10^11 M_⊙) galaxies from the near-infrared Palomar/DEEP-2 survey, we explore what fraction of these objects have satellites with 0.01 < M_sat/M_central < 1 (1:100) up to z= 1 and what fraction have satellites with 0.1 < M_sat/M_central < 1 (1:10) up to z= 2 within a projected radial distance of 100 kpc. We find that the fraction of massive galaxies with satellites, after background correction, remains basically constant and close to 30 per cent for satellites with a mass ratio down to 1:100 up to z= 1, and close to 15 per cent for satellites with a 1:10 mass ratio up to z= 2. The family of spheroid-like massive galaxies presents a 2–3 times larger fraction of objects with satellites than the group of disc-like massive galaxies. A crude estimation of the number of 1:3 mergers a massive spheroid-like galaxy has experienced since z~2 is around 2. For a disc-like galaxy this number decreases to ~1.

Measuring star formation in high-z massive galaxies: a mid-infrared to submillimetre study of the GOODS NICMOS Survey sample

We present measurements of the mean mid-infrared to submillimetre flux densities of massive (M_*≳ 10^11 M_⊙) galaxies at redshifts 1.7 < z < 2.9, obtained by stacking positions of known objects taken from the GOODS NICMOS Survey (GNS) catalogue on maps at 24 μm (Spitzer/MIPS); 70, 100 and 160 μm (Herschel/PACS); 250, 350 and 500 μm (BLAST); and 870 μm (LABOCA). A modified blackbody spectrum fit to the stacked flux densities indicates a median [interquartile] star formation rate (SFR) of SFR = 63[48, 81] M_⊙ yr^−1. We note that not properly accounting for correlations between bands when fitting stacked data can significantly bias the result. The galaxies are divided into two groups, disc-like and spheroid-like, according to their Sérsic indices, n. We find evidence that most of the star formation is occurring in n≤ 2 (disc-like) galaxies, with median [interquartile] SFR = 122[100, 150] M_⊙ yr^−1, while there are indications that the n > 2 (spheroid-like) population may be forming stars at a median [interquartile] SFR = 14[9, 20] M_⊙ yr^−1, if at all. Finally, we show that star formation is a plausible mechanism for size evolution in this population as a whole, but find only marginal evidence that it is what drives the expansion of the spheroid-like galaxies.

PEDOT:PSS thin films: Applications in Bioelectronics

Owing to their capability of merging the properties of metals and conventional polymers, Conducting Polymers (CPs) are a unique class of carbon-based materials capable of conducting electrical current. A conjugated backbone is the hallmark of CPs, which can readily undergo reversible doping to different extents, thus achieving a wide range of electrical conductivities, while maintaining mechanical flexibility, transparency and high thermal stability. Thanks to these inherent versatility and attracting properties, from their discovery CPs have experienced incessant widespread in a great plethora of research fields, ranging from energy storage to healthcare, also encouraging the spring and growth of new scientific areas with highly innovative content. Nowadays, Bioelectronics stands out as one of the most promising research fields, dealing with the mutual interplay between biology and electronics. Among CPs, the polyelectrolyte complex poly (3,4-ethylenedioxythiophene): poly (styrenesulfonate) (PEDOT:PSS), especially in the form of thin films, has been emphasized as ideal platform for bioelectronic applications. Indeed, in the last two decades PEDOT:PSS has played a key role in the sensing of bioanalytes and living cells interfacing and monitoring. In the present work, development and characterization of two kinds of PEDOT:PSS-based devices for applications in Bioelectronics are discussed in detail. In particular, a low-cost amperometric sensor for the selective detection of Dopamine in a ternary mixture was optimized, taking advantage of the electrocatalytic and antifouling properties that render PEDOT:PSS thin films appealing tools for electrochemical sensing of bioanalytes. Moreover, the potentialities of this material to interact with live cells were explored through the fabrication of a microfluidic trapping device for electrical monitoring of 3D spheroids using an impedance-based approach.

ELEMENTOS DE CARTOGRAFÍA MATEMÁTICA Y SU APLICACIÓN EN LA ELABORACIÓN DE LAS CARTAS GEOGRÁFICAS

En este artículo se analizan algunos de los elementos básicos de la cartografía matemática, partiendo de los aspectos generales como sistemas de coordenadas y superficies de referencia. Se discuten además los elementos cartográficos sobre los esferoides, los datums y la definición de los sistemas de coordenadas geográficas, así como las transformaciones esferoidales. Una vez establecidos los conceptos básicos, se discuten los aspectos fundamentales de la teoría de las proyecciones cartográficas y sus principales características.ABSTRACTThis article analyzes some basic concepts about mathematical cartography, from general aspects such as coordinate systems and reference surfaces. The cartographic elements concerning spheroids, datum and definitions of geographical coordinate systems are discussed, as well as the spheroid transformations. Based on these basic concepts, the fundamental aspects of cartographic projections theory and its main characteristics are discussed.

Development of an impedance based biosensor for studies of spheroids formation

Three-dimensional (3D) multicellular spheroids are exceptional in vitro cell models for their ability to accurately mimic real cell-cell interaction processes. However, the challenges in producing well-defined spheroids with controlled size together with the deficiency of techniques to monitor them significantly restrict their use. Herein, a novel device to study spheroid formation in real time is presented. By exploiting electrochemical impedance spectroscopy, a multi-electrode array (MEA) attached to a calcium alginate scaffold is able to monitor the behaviour of 36 different hydrogel wells. The scaffold contains inverted shape pyramidal microwells, which guide the aggregation of cells into spheroids with controlled dimensions. Preliminar studies on calcium alginate, optimisation of fabrication strategy are shown, together with testing of the device in the presence and the absence of the hydrogel. Lastly, the device was tested for its intended aim, i.e. to monitor the formation of a spheroid, proving its potential as an impedance biosensor.

Stellar mass loss from the Fornax dwarf spheroidal galaxy

Dwarf galaxies often experience gravitational interactions from more massive companions. These interactions can deform galaxies, turn star formation on or off, or give rise to mass loss phenomena. In this thesis work we propose to study, through N-body simulations, the stellar mass loss suffered by the dwarf spheroid galaxy (dSph) Fornax orbiting in the Milky Way gravitational potential. Which is a key phenomenon to explain the mass budget problem: the Fornax globular clusters together have a stellar mass comparable to that of Fornax itself. If we look at the stellar populations which they are made of and we apply the scenarios of stellar population formation we find that, originally, they must have been >= 5 times more massive. For this reason, they must have lost or ejected stars through dynamic interactions. However, as presented in Larsen et al (2012), field stars alone are not sufficient to explain this scenario. We may assume that some of those stars fell into Fornax, and later were stripped by Milky Way. In order to study this solution we built several illustrative single component simulations, with a tabulated density model using the P07ecc orbit studied from Battaglia et al (2015). To divide the single component into stellar and dark matter components we have defined a posterior the probability function P(E), where E is the initial energy distribution of the particles. By associating each particle with a fraction of stellar mass and dark matter. In this way we built stellar density profiles without repeating simulations. We applied the method to Fornax using the profile density tables obtained in Pascale et al (2018) as observational constraints and to build the model. The results confirm the results previously obtained with less flexible models by Battaglia et al (2015). They show a stellar mass loss < 4% within 1.6 kpc and negligible within 3 kpc, too small to solve the mass budget problem.