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Observing an intermediate mass black hole GW190521 with minimal assumptions

Szczepanczyk Marek, Klimenko Sergey, O'Brien Brendan, Bartos Imre, Gayathri V., Mitselmakher Guenakh, Prodi Giovanni, Vedovato Gabriele, Lazzaro Claudia, Milotti Edoardo
23 Sep 2020 astro-ph.HE arxiv.org/abs/2009.11336

On May 21, 2019 Advanced LIGO and Advanced Virgo detectors observed a gravitational-wave transient GW190521, the heaviest binary black-hole merger detected to date with the remnant mass of 142$\,$M$_\odot$ that was published recently. This observation is the first strong evidence for the existence of intermediate-mass black holes. The significance of this observation was determined by the coherent WaveBurst (cWB) - search algorithm, which identified GW190521 with minimal assumptions on its source model. In this paper, we demonstrate the capabilities of cWB to detect binary black holes without use of the signal templates, describe the details of the GW190521 detection and establish the consistency of the model-agnostic reconstruction of GW190521 by cWB with the theoretical waveform model of a binary black hole.

Fine-grained simulations of the microenvironment of vascularized tumours

Fredrich Thierry, Rieger Heiko, Chignola Roberto, Milotti Edoardo
06 Jun 2019 physics.bio-ph arxiv.org/abs/1906.02441

One of many important features of the tumour microenvironment is that it is a place of active Darwinian selection where different tumour clones become adapted to the variety of ecological niches that make up the microenvironment. These evolutionary processes turn the microenvironment into a powerful source of tumour heterogeneity and contribute to the development of drug resistance in cancer. Here, we describe a computational tool to study the ecology of the microenvironment and report results about the ecology of the tumour microenvironment and its evolutionary dynamics.

Polarization observables for millicharged particles in photon collisions

Gabrielli Emidio, Marzola Luca, Milotti Edoardo,
01 Apr 2016 hep-ph arxiv.org/abs/1604.00393

Particles in a hidden sector can potentially acquire a small electric charge through their interaction with the Standard Model and can consequently be observed as millicharged particles. We systematically compute the production of millicharged scalar, fermion and vector boson particles in collisions of polarized photons. The presented calculation is model independent and is based purely on the assumptions of electromagnetic gauge invariance and unitarity. Polarization observables are evaluated and analyzed for each spin case. We show that the photon polarization asymmetries are a useful tool for discriminating between the spins of the produced millicharged particles. Phenomenological implications for searches of millicharged particles in dedicated photon-photon collision experiments are also discussed.

Bridging the gap between the micro- and the macro-world of tumors

Chignola Roberto, Milotti Edoardo
13 Jan 2012 q-bio.TO physics.bio-ph q-bio.CB arxiv.org/abs/1201.2798

At present it is still quite difficult to match the vast knowledge on the behavior of individual tumor cells with macroscopic measurements on clinical tumors. On the modeling side, we already know how to deal with many molecular pathways and cellular events, using systems of differential equations and other modeling tools, and ideally, we should be able to extend such a mathematical description up to the level of large tumor masses. An extended model should thus help us forecast the behavior of large tumors from our basic knowledge of microscopic processes. Unfortunately, the complexity of these processes makes it very difficult -- probably impossible -- to develop comprehensive analytical models. We try to bridge the gap with a simulation program which is based on basic biochemical and biophysical processes -- thereby building an effective computational model -- and in this paper we describe its structure, endeavoring to make the description sufficiently detailed and yet understandable.

Measuring the magnetic birefringence of vacuum: the PVLAS experiment

Zavattini Guido, Gastaldi Ugo, Pengo Ruggero, Ruoso Giuseppe, Della Valle Federico, Milotti Edoardo
11 Jan 2012 hep-ex quant-ph arxiv.org/abs/1201.2309

We describe the principle and the status of the PVLAS experiment which is presently running at the INFN section of Ferrara, Italy, to detect the magnetic birefringence of vacuum. This is related to the QED vacuum structure and can be detected by measuring the ellipticity acquired by a linearly polarized light beam propagating through a strong magnetic field. Such an effect is predicted by the Euler-Heisenberg Lagrangian. The method is also sensitive to other hypothetical physical effects such as axion-like particles and in general to any fermion/boson millicharged particle. Here we report on the construction of our apparatus based on a high finesse ($>2\cdot10^5$) Fabry-Perot cavity and two 0.9 m long 2.5 T permanent dipole rotating magnets, and on the measurements performed on a scaled down test setup. With the test setup we have improved by about a factor 2 the limit on the parameter $A_e$ describing non linear electrodynamic effects in vacuum: $A_e < 2.9\cdot10^{-21}$ T$^{-2}$ @ 95% c.l.

Computational challenges of tumor spheroid modeling

Chignola Roberto, Del Fabbro Alessio, Farina Marcello, Milotti Edoardo
09 Dec 2010 q-bio.TO arxiv.org/abs/1012.2125

The speed and the versatility of today's computers open up new opportunities to simulate complex biological systems. Here we review a computational approach recently proposed by us to model large tumor cell populations and spheroids, and we put forward general considerations that apply to any fine-grained numerical model of tumors. We discuss ways to bypass computational limitations and discuss our incremental approach, where each step is validated by experimental observations on a quantitative basis. We present a few results on the growth of tumor cells in closed and open environments and of tumor spheroids. This study suggests new ways to explore the initial growth phase of solid tumors and to optimize anti-tumor treatments.

Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Milotti Edoardo, Chignola Roberto
10 Oct 2010 q-bio.TO physics.bio-ph physics.comp-ph physics.med-ph arxiv.org/abs/1010.1965

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.

Ab initio computational modeling of tumor spheroids

Chignola Roberto, Del Fabbro Alessio, Farina Marcello, Milotti Edoardo
03 Nov 2009 q-bio.CB q-bio.PE arxiv.org/abs/0911.0596

This paper is a review of the VBL project, where we develop and test a numerical simulator of tumor spheroids.

Dynamics of intracellular Ca$^{2+}$ oscillations in the presence of multisite Ca$^{2+}$-binding proteins

Chignola Roberto, Del Fabbro Alessio, Milotti Edoardo
10 Sep 2009 q-bio.SC arxiv.org/abs/0909.1918

We study the dynamics of intracellular calcium oscillations in the presence of proteins that bind calcium on multiple sites and that are generally believed to act as passive calcium buffers in cells. We find that multisite calcium-binding proteins set a sharp threshold for calcium oscillations. Even with high concentrations of calcium-binding proteins, internal noise, which shows up spontaneously in cells in the process of calcium wave formation, can lead to self-oscillations. This produces oscillatory behaviors strikingly similar to those observed in real cells. In addition, for given intracellular concentrations of both calcium and calcium-binding proteins the regularity of these oscillations changes and reaches a maximum as a function noise variance, and the overall system dynamics displays stochastic coherence. We conclude that calcium-binding proteins may have an important and active role in cellular communication.

Balance between cell survival and death: a minimal quantitative model of tumor necrosis factor alpha cytotoxicity

Chignola Roberto, Farina Marcello, Del Fabbro Alessio, Milotti Edoardo
27 May 2009 q-bio.MN q-bio.CB arxiv.org/abs/0905.4396

Tumor Necrosis Factor alpha (TNF) initiates a complex series of biochemical events in the cell upon binding to its type R1 receptor (TNF-R1). Recent experimental work has unravelled the molecular regulation of the recruitment of initial signaling complexes that lead either to cell survival or death. Survival signals are activated by direct binding of TNF to TNF-R1 at the cell membrane whereas apoptotic signals by endocytosed TNF/TNF-R1 complexes. Here we investigate these aspects by developing a quantitative mathematical model of TNF binding, internalization and intracellular signaling. Model outputs compare favorably with experimental data and allow to compute TNF-mediated cytotoxicity as observed in different cell systems. We extensively study the space of parameters to show that the model is structurally stable and robust over a broad range of parameter values. Thus, our model is suitable for implementation in multi-scale simulation programs that are presently under development to study the behavior of large tumor cell populations.