Induction of Epithelial-Mesenchymal Transition (EMT) in women´s cancer : protective role of differentiation factors

Metastatic spread of cancer cells to vital organs is the predominant cause of death among women suffering from breast and ovarian cancer, and invasive cancer cells are in many cases resilient to standard drugs used in the clinic. Consequently, further understanding of the metastatic process and development of new strategies to target invasive cancer cells are needed. One process that has been closely linked to cancer cell invasion and migration is epithelial-mesenchymal transition (EMT), a developmental process, which can be reactivated during cancer progression. EMT allows carcinoma cells, with an epithelial origin, to acquire mesenchymal and migratory properties that are employed to invade the surrounding tumor tissue. The overall aim of this thesis was to investigate how EMT is induced in breast and ovarian cancer cells and to study the role of EMT in drug resistance. Relapse of resilient cancer cells after surgery and first line of drug treatments is a major cause of death in ovarian and breast cancer. Currently, little is known about the functional properties of cancer cells that develop resistance to existing drug treatments and how they can be targeted. The aim of study I was to characterize the phenotypic properties of ovarian cancer cells that developed resistance to cisplatin, a chemotherapeutic drug commonly used in the clinic. We found that human SKOV-3 ovarian cancer cells that acquired resistance to cisplatin gained properties of EMT and cancer stem cells, suggesting that they were more invasive than drug-sensitive cells. Indeed, functional experiments showed that cisplatin-resistant SKOV-3 cells were more migratory in invasion assays and displayed an increased tumor initiating capacity compared to cisplatin-sensitive cells. The results from these studies link EMT to drug resistance in ovarian cancer cells, and emphasize that further understanding of EMT is needed and to be able to target EMT for therapy. In study II-IV we investigated how cellular sensitivity to EMT is regulated. In particular, we focused on identifiying epithelial differentiation factors that regulate EMT in breast cancer cells. We identified two transcription factors – C/EBPβ and Foxp4 that were lost during breast cancer progression, which conferred cells an enhanced capacity to undergo EMT as well as to gain invasive and metastatic properties in experimental in vitro and in vivo models of breast cancer. In addition, we identified the coxsackie- and adenovirus receptor (CAR), a tight junction-based cell adhesion molecule, as a novel regulator of Akt signaling and TGF-β-induced EMT in breast cancer cells. The mechanism was traced to a role of CAR in regulating localization, stability and function of the phosphatase Pten, a potent Akt inhibitor, at tight junctions. The results from these studies indicate that the EMT process is not solely regulated by factors that drive a mesenchymal differentiation program, but also, is under tight control by epithelial differentiation factors. Loss of C/EBPβ, Foxp4 and CAR may lead to increased cellular sensitivity to EMT and thereby open up the possibility that cancer cells acquire invasive and migratory properties. Based on this, we propose that novel therapies aiming to strengthen, or preserve, epithelial differentiation mechanisms in breast or ovarian cancer cells, might be useful as a type of differentiation therapy to inhibit cancer cell invasion and metastasis

Motion and gravity effects in the precision of quantum clocks

We show that motion and gravity affect the precision of quantum clocks. We consider a localised quantum field as a fundamental model of a quantum clock moving in spacetime and show that its state is modified due to changes in acceleration. By computing the quantum Fisher information we determine how relativistic motion modifies the ultimate bound in the precision of the measurement of time. While in the absence of motion the squeezed vacuum is the ideal state for time estimation, we find that it is highly sensitive to the motion-induced degradation of the quantum Fisher information. We show that coherent states are generally more resilient to this degradation and that in the case of very low initial number of photons, the optimal precision can be even increased by motion. These results can be tested with current technology by using superconducting resonators with tunable boundary conditions.Comment: 10 pages, 6 figures. I. F. previously published as I. Fuentes-Guridi and I. Fuentes-Schulle

Scattering of coherent pulses on a two-level system-single-photon generation

In this paper, we consider a two-level system (TLS) coupled to a one-dimensional continuum of bosonic modes in a transmission line (TL). Using the master equation approach, a method for determining the photon number distribution of the scattered field is outlined. Specifically, results for the reflected field when driving the TLS with a coherent pulse are given. While the one-photon probability is enhanced compared to the incident coherent field, the system is still not a good deterministic single-photon source. Extending the system to contain two separate TLs, however, output fields with one-photon probabilities close to unity can be reached

Non-resonant multipactor - A statistical model

High power microwave systems operating in vacuum or near vacuum run the risk of multipactor breakdown. In order to avoid multipactor, it is necessary to make theoretical predictions of critical parameter combinations. These treatments are generally based on the assumption of electrons moving in resonance with the electric field while traversing the gap between critical surfaces. Through comparison with experiments, it has been found that only for small system dimensions will the resonant approach give correct predictions. Apparently, the resonance is destroyed due to the statistical spread in electron emission velocity, and for a more valid description it is necessary to resort to rather complicated statistical treatments of the electron population, and extensive simulations. However, in the limit where resonance is completely destroyed it is possible to use a much simpler treatment, here called non-resonant theory. In this paper, we develop the formalism for this theory, use it to calculate universal curves for the existence of multipactor, and compare with previous results. Two important effects that leads to an increase in the multipactor threshold in comparison with the resonant prediction are identified. These are the statistical spread of impact speed, which leads to a lower average electron impact speed, and the impact of electrons in phase regions where the secondary electrons are immediately reabsorbed, leading to an effective removal of electrons from the discharge

Understanding the Structural Scaling Relations of Early-Type Galaxies

We use a large suite of hydrodynamical simulations of binary galaxy mergers to construct and calibrate a physical prescription for computing the effective radii and velocity dispersions of spheroids. We implement this prescription within a semi-analytic model embedded in merger trees extracted from the Bolshoi Lambda-CDM N-body simulation, accounting for spheroid growth via major and minor mergers as well as disk instabilities. We find that without disk instabilities, our model does not predict sufficient numbers of intermediate mass early-type galaxies in the local universe. Spheroids also form earlier in models with spheroid growth via disk instabilities. Our model correctly predicts the normalization, slope, and scatter of the low-redshift size-mass and Fundamental Plane relations for early type galaxies. It predicts a degree of curvature in the Faber-Jackson relation that is not seen in local observations, but this could be alleviated if higher mass spheroids have more bottom-heavy initial mass functions. The model also correctly predicts the observed strong evolution of the size-mass relation for spheroids out to higher redshifts, as well as the slower evolution in the normalization of the Faber-Jackson relation. We emphasize that these are genuine predictions of the model since it was tuned to match hydrodynamical simulations and not these observations.Comment: Submitted to MNRA

Classification dynamique d'un flux documentaire : une évaluation statique préalable de l'algorithme GERMEN.

International audienceData-stream clustering is an ever-expanding subdomain of knowledge extraction. Most of the past and present research effort aims at efficient scaling up for the huge data repositories. Our approach focuses on qualitative improvement, mainly for "weak signals" detection and precise tracking of topical evolutions in the framework of information watch - though scalability is intrinsically guaranteed in a possibly distributed implementation. Our GERMEN algorithm exhaustively picks up the whole set of density peaks of the data at time t, by identifying the local perturbations induced by the current document vector, such as changing cluster borders, or new/vanishing clusters. Optimality yields from the uniqueness 1) of the density landscape for any value of our zoom parameter, 2) of the cluster allocation operated by our border propagation rule. This results in a rigorous independence from the data presentation ranking or any initialization parameter. We present here as a first step the only assessment of a static view resulting from one year of the CNRS/INIST Pascal database in the field of geotechnics

BRICHOS - a superfamily of multidomain proteins with diverse functions

ABSTRACT: BACKGROUND: The BRICHOS domain has been found in 8 protein families with a wide range of functions and a variety of disease associations, such as respiratory distress syndrome, dementia and cancer. The domain itself is thought to have a chaperone function, and indeed three of the families are associated with amyloid formation, but its structure and many of its functional properties are still unknown. FINDINGS: The proteins in the BRICHOS superfamily have four regions with distinct properties. We have analysed the BRICHOS proteins focusing on sequence conservation, amino acid residue properties, native disorder and secondary structure predictions. Residue conservation shows large variations between the regions, and the spread of residue conservation between different families can vary greatly within the regions. The secondary structure predictions for the BRICHOS proteins show remarkable coherence even where sequence conservation is low, and there seems to be little native disorder. CONCLUSIONS: The greatly variant rates of conservation indicates different functional constraints among the regions and among the families. We present three previously unknown BRICHOS families; group A, which may be ancestral to the ITM2 families; group B, which is a close relative to the gastrokine families, and group C, which appears to be a truly novel, disjoint BRICHOS family. The C-terminal region of group C has nearly identical sequences in all species ranging from fish to man and is seemingly unique to this family, indicating critical functional or structural properties.Original Publication:Joel Hedlund, Jan Johansson and Bengt Persson, BRICHOS - a superfamily of multidomain proteins with diverse functions., 2009, BMC research notes, (2), 180.http://dx.doi.org/10.1186/1756-0500-2-180Licensee: BioMed Centralhttp://www.biomedcentral.com

Twin paradox with macroscopic clocks in superconducting circuits

We propose an implementation of a twin paradox scenario in superconducting circuits, with velocities as large as a few percent of the speed of light. Ultrafast modulation of the boundary conditions for the electromagnetic field in a microwave cavity simulates a clock moving at relativistic speeds. Since our cavity has a finite length, the setup allows us to investigate the role of clock size as well as interesting quantum effects on time dilation. In particular, our theoretical results show that the time dilation increases for larger cavity lengths and is shifted due to quantum particle creation.Comment: 6 pages, 3 figures. I. F. previously published as I. Fuentes-Guridi and I. Fuentes-Schulle

LFV:s investeringsmodell

In the last few years the airline industry had experienced a rapid growth within the low cost segment. The expenses for the airline companies have during the same period increased, mostly due to higher fuel prices and higher capital costs for airplanes. As a result of this, the economic situation for the airline companies has come to be very strained. The Swedish Civil Aviation Authority (LFV), which runs 17 airports and all air traffic control in Sweden, has been required to lower its cost in order to facilitate a further expansion of low cost air travel. A great number of vehicles used at LFV airports are fairly advanced in years and therefore also have a low reliability. This is especially true regarding the snow clearing vehicles of which some are older than 30 years and consequently requires extensive maintenance. Reports indicate that there are savings to be made by better and more efficient management of the airport vehicles. One explanation to why airport vehicles systematically have been set aside in the priority between different investments might be found in the model LFV is using to evaluate new investments. The purpose of this report is therefore to describe the current investment model that LFV is using to evaluate investments in snow clearing vehicles. This report is limited to explain the investment model strictly from a business economy perspective. Factors such as environmental aspects or image will not be dealt with. The concluding discussion about making changes to the investment model is assuming that the adapted model will be used to evaluate investments in airport vehicles only. This report could be referred to as a descriptive study of qualitative nature. Today LFV is using an investment model which automatically calculates the key values of the investment studied. In order to evaluate investments and make priorities between them the LFV is referring to the internal rate of return (IRR). The IRR is presented in the investment model together with the net present value (NPV) and the pay back time. These three key values represent the basic information about the investments economic consequences. In addition to these key values the investment model also allows compensation for inflation and evaluation of different future scenarios. The discount rate for the investments is based on the cost for LFV’s debt, but is not calculated within the investment model. Generally LFV’s investment model is working as expected and all calculations are performed correctly. There are however some exceptions regarding calculation with the discount rate. These calculations are not done in the correct manner and the result of this is that the numbers presented are slightly more pessimistic than they should be. When it comes to evaluation of new investments in airport vehicles an adaptation of the investment model could result in better information about the economic consequences of such investments. Initially the calculations including discount rates should be corrected letting the investment model present the correct economic results. A discount rate related to the level of risk of the investment could make low-risk investments seem more profitable. This would probably favour investments such as airport vehicles since these are associated with a relatively low risk. Also, considering the investments different requirement of capital and the tax consequences would further improve the economic information which the investment decisions are based upon