maria grazia pia, infn genova for microdosimetry for microdosimetry cecam workshop lyon, 3-6...

Maria Grazia Pia, INFN Genova

forfor MicrodosimetryMicrodosimetry

CECAM WorkshopLyon, 3-6 December 2007

DNADNA

Maria Grazia PiaINFN Genova

S. Chauvie (Cuneo Hospital and INFN), S. Incerti and Ph. Moretto (CENBG)

Partly funded by

Maria Grazia Pia, INFN GenovaCourtesy Borexino

Courtesy H. Araujo and A. Howard, IC London

ZEPLIN III

Courtesy CMS Collaboration

Courtesy ATLAS Collaboration

Courtesy K. Amako et al., KEK

Courtesy GATE Collaboration

Courtesy R. Nartallo et al.,ESA

Widely used also in Space science and astrophysics Medical physics, nuclear medicine Radiation protection Accelerator physics Humanitarian projects, security etc.Technology transfer to industry, hospitals…

Born from the requirements of large scale HEP experiments

Most cited Most cited “Nuclear Science “Nuclear Science and Technology” and Technology”

publication!publication!

S. Agostinelli et al.GEANT4 - a simulation toolkit

NIM A 506 (2003) 250-303


LHC

ATLAS

LHCb

Complex physicsComplex physicsComplex detectorsComplex detectors

20 years software life-span


DosimetryDosimetry

Space scienceRadiotherapy Effects on components

Multi-disciplinary application environmentMulti-disciplinary application environment

Wide spectrum of physics coverage, variety of physics modelsPrecise, quantitatively validated physics

Accurate description of geometry and materials

Courtesy of ESACourtesy of CERN RADMON team


Dosimetry Dosimetry in Medicalin Medical ApplicationsApplications

Courtesy of L. Beaulieu et al., Laval

BrachytherapyRadiation Protection

Courtesy of J. Perl, SLAC

Hadrontherapy

Courtesy of P. Cirrone et al., INFN LNS

Courtesy of F. Foppiano et al,. IST and INFN Genova

Radiotherapy with external beams, IMRT

Courtesy of F. Foppiano et al., IST and INFN Genova


Exotic Geant4 applications…Exotic Geant4 applications…

FAO/IAEA International Conference on Area-Wide Control of Insect PestsArea-Wide Control of Insect Pests:

Integrating the Sterile Insect and Related Nuclear and Other Techniques

Vienna, May 9-13, 2005

K. Manai, K. Farah, A.Trabelsi, F. Gharbi and O. Kadri (Tunisia)

Dose Distribution and Dose Uniformity in Pupae Treated by the Tunisian Gamma Irradiator Using the GEANT4 Toolkit


Precise dose calculationPrecise dose calculationGeant4 Low Energy Electromagnetic Physics Geant4 Low Energy Electromagnetic Physics

packagepackageElectrons and photons (250/100 eV < E < 100 GeV)

Models based on the Livermore libraries (EEDL, EPDL, EADL) Models à la Penelope

Hadrons and ions Free electron gas + Parameterisations (ICRU49, Ziegler) + Bethe-Bloch Nuclear stopping power, Barkas effect, chemical formula, effective charge etc.

Atomic relaxation Fluorescence, Auger electron emission, PIXE

Fe lines

GaAs lines

Atomic relaxationFluorescence

Auger effectshell effectsions


Fundamental concepts

Functionality: Functionality: physics, geometry etc.physics, geometry etc.Functionality: Functionality: physics, geometry etc.physics, geometry etc.

Software technologySoftware technologySoftware technologySoftware technology

Open source distributionOpen source distributionOpen source distributionOpen source distribution

Toolkit Toolkit Toolkit Toolkit

TransparencyTransparencyTransparencyTransparency

International CollaborationInternational CollaborationInternational CollaborationInternational Collaboration


PhysicsPhysicsFrom the Minutes of LCB (LHCC Computing Board) meeting on 21 October, 1997:

“It was noted that experiments have requirements for independent, alternative physics models. In Geant4 these models, differently from the concept of packages, allow the user to understandunderstand how the results are produced, and hence improve the physics validationphysics validation. Geant4 is developed with a modular architecture and is the ideal framework where existing components are integrated and new models continue to be developed.”


Domain decomposition

hierarchical structure of sub-

domains

Geant4 architecture

Uni-directional flow of

dependencies

Interface to external products w/o dependencies

Software EngineeringSoftware Engineeringplays a fundamental role in Geant4

User Requirements• formally collected• systematically updated• PSS-05 standard

Software Process• spiral iterative approach• regular assessments and improvements (SPI process)• monitored following the ISO 15504 model

Quality Assurance• commercial tools• code inspections• automatic checks of coding guidelines• testing procedures at unit and integration level• dedicated testing team

Object Oriented methods • OOAD• use of CASE tools

• openness to extension and evolution• contribute to the transparency of physics• interface to external software without dependencies

Use of Standards • de jure and de facto


ToolkitToolkitA set of compatible componentscomponents

each component is specialisedspecialised for a specific functionalityeach component can be refinedrefined independently to a great detailcomponents can be integratedintegrated at any degree of complexityit is easy to provide (and use) alternativealternative componentsthe user application can be customisedcustomised as needed

Openness to extensionextension and evolution evolution new implementations can be added w/o changing the existing code

Robustness and ease of maintenancemaintenance

protocolsprotocols and well defined dependenciesdependencies minimize coupling

OO OO technologytechnology

Strategic Strategic visionvision


http://www.ge.infn.it/geant4/dnahttp://www.ge.infn.it/geant4/dna


Biological models in Geant4 Biological models in Geant4

Relevance for space: Relevance for space: astronaut and aircrew radiation hazardsastronaut and aircrew radiation hazards

Project originally motivated and partly funded by


Simulation of nano-scale effects of radiation at the DNA level Various scientific domains involved

medical, biology, genetics, physics, software engineering

Multiple approaches can be implemented with Geant4 RBE parameterisation, detailed biochemical processes, etc.

First phase: 2000-2001 Collection of user requirements & first prototypes

Second phase: started in 2004 Software development & open source release

DNADNA “Sister” activity to Geant4 Low-Energy Electromagnetic PhysicsGeant4 Low-Energy Electromagnetic PhysicsFollows the same rigorous software standards

INFN (Genova) - IN2P3 (CENBG)Partly sponsored by ESA

New collaborators welcome!


MultipleMultiple domains in the domains in the samesame software software environmentenvironment

Macroscopic levelMacroscopic level calculation of dose

already feasible with Geant4

develop useful associated tools

Cellular level cell modelling

processes for cell survival, damage etc.

DNA level DNA modelling

physics processes at the eV scale

bio-chemical processes

processes for DNA damage, repair etc.

Complexity of

software, physics and biologysoftware, physics and biology

addressed with an iterative and incremental software process

Parallel development at all the three levels

(domain decomposition)


What’s new?What’s new?Many “track structure” Monte Carlo codes previously developed A lot of modelling expertise embedded in these codes Each code implements oneone modelling approach (developed by its authors) “Stand-aloneStand-alone” codes, with limited application scope Legacy software technology (FORTRAN, procedural programming) Not publicly distributedNot publicly distributed

Geant4-DNAGeant4-DNA “Track structure” simulation in a general-purpose Monte Carlo system Toolkit approach: many interchangeable models Advanced software technology Rigorous software process software process Open sourceOpen source, freely available, supported by an international organization Foster a collaborative spirit in the scientific community Benefit of the feedback of a wider user community


11stst development cycle: development cycle:

Geant4 physics Geant4 physics extensionsextensions

Complex domain Physics: collaboration with theorists

Technology: innovative design technique introduced in Geant4

(1st time in Monte Carlo)

Experimental complexity as well Scarce experimental data

Collaboration with experimentalists for model validation

Geant4 physics validation at low energies is difficult!

Physics down to the eV scalePhysics down to the eV scale


Geant4-DNA physics Geant4-DNA physics processesprocesses

Models in liquid water More realistic than water vapour

Theoretically more challenging

Hardly any experimental data

New measurements needed

Status 1st -release Geant4 8.1

Full release on 14 December 2007

Further extensions in progress Models for water vapour

Models for other materials than water

Particle Processes

e-Elastic scatteringExcitationIonisation

pCharge decreaseExcitationIonisation

H Charge increaseIonisation

He++Charge decreaseExcitationIonisation

He+

Charge decreaseCharge increaseExcitationIonisation

HeCharge increaseExcitationIonisation

Specialised processes for low energy interactions with water


(Current) Physics Models(Current) Physics Models

e p H He+ HeElastic > 7.5 eV

Screened Rutherford + empirical

Brenner-Zaider

Excitation 7.5 eV – 10 keVA1B1, B1A1, Ryd A+B, Ryd C+D,

diffuse bands

10 eV – 500 keVDingfelder

500 keV – 10 MeVEmfietzoglou

100 eV – 10 MeVDingfelder Effective

charge scaling from same

models as for proton

Dingfelder

Charge Change

100 eV – 10 MeVDingfelder


Ionisation7 eV – 10 keVEmfietzoglou

1b1, 3a1, 1b2, 2a1 + 1a1

100 eV – 500 keVRudd

500 keV – 10 MeVDingfelder (Born)



Why these models?Why these models?No emotional attachment to any of the models Toolkit: offer a wide choice among many available alternatives

Complementary/alternative models

No “one size fits all”

Powerful design Abstract interfaces: the kernel is blind to any specific modelling

The system is intrinsically open to multiple implementations

Improvements, extensions, options Open system

Collaboration is welcome (experimental/modelling/software)


What is behind…What is behind…A policy defines a class or class template interface

Policy host classes are parameterised classes classes that use other classes as a parameter

Advantage w.r.t. a conventional strategy pattern Policies are not required to inherit from a base class

The code is bound at compilation time No need of virtual methods, resulting in faster execution

Policy-based Policy-based class designclass design

Policies can proliferate w/o any limitation

Syntax-oriented rather than signature-oriented

New technique

1st time introduced in Monte

Carlo

Weak dependency of the policy and the policy based class on the policy interface

Highly customizable designOpen to extension


Geant4-DNA physics processGeant4-DNA physics process

Deprived of any intrinsic physics functionality

Configured by

template specializationtemplate specialization to acquire physics properties

Handled transparently by Geant4 kernel


Development metricsDevelopment metricsOpen to extension: what does it mean in practice?

Implementation + unit test of a new physics model ~ 5 to 7 hours5 to 7 hours (average computing experience) No integration effort at all

Other software processes Peer review of the code Integration testing System testing Porting to other supported platforms User documentation Experimental validation

Investment in software technology!Investment in software technology!


More details on both software and physics in IEEE Trans. Nucl. Sci., IEEE Trans. Nucl. Sci., Vol. 54, no. 6, Dec. 2007Vol. 54, no. 6, Dec. 2007


Example of simulationExample of simulation

Liquid water sphere

0.2 µm diameter

1000 electrons shot from central source

E = 20 keV

Geant4 physics processes:

Elastic scattering

Excitation

Ionisation

0.2 µm

Shower of particles at

the nm / eV scale


How How accurate accurate are are Geant4-DNA physics Geant4-DNA physics models ?models ?

Both theoretical and experimental complexity in the very low energy régime

Theoretical calculations must take into account the detailed dielectric structure of the interacting material Approximations, assumptions, semi-empirical models

Experimental measurements are difficult Control of systematics

Practical constraints depending on the phase


Verification & ValidationVerification & Validation

Verification Conformity with theoretical models

Performed on all physics models

Validation Against experimental data

Lack of experimental data in liquid water in the very low energy range

New measurements needed

Evaluation of plausibility Only practical option at the present stage

Comparison against experimental data in water vapour/ice

Interesting also to study phase-related effects


A selection of resultsA selection of results

Systematic comparison in progress Survey of literature: extensive collection of experimental data

(goal: all!)

No time to show all of them ( paper)

Selection of a few interesting cases Highlight the complexity of the experimental domain

Discuss physics modelling features

S. Chauvie, S. Incerti, P. Moretto, M. G. Pia, Evaluation of Phase Effects in Geant4 Microdosimetry Models for Particle Interactions in Water, Proc. IEEE NSS 2007


Electron elastic scatteringElectron elastic scatteringTheoretical challenge to model accurately at very low energy

Various theoretical approaches at different degrees of complexity From simple screened Rutherford cross section to sophisticated phase shift

calculations

No experimental data in liquid water

Geant4-DNA Simple screened Rutherford cross section + semi-empirical model based on

vapour data

(Why so unsophisticated? Look at the experimental data…)

Open to evolution along with the availability of new data


Electron elastic scattering: Electron elastic scattering: total cross sectiontotal cross section

Evident discrepancy of the experimental data

Puzzle: inconsistency in recommended evaluated data from Itikawa & Mason, J. Phys. Chem. Ref. Data, 34-1, pp. 1-22, 2005.

Geant4-DNA Better agreement with some of

the data sets

Hardly conclusive comparison, given the experimental status…

Geant4-DNA elastic Itikawa & Mason elastic (recommended) Itikawa & Mason total (recommended) Danjo & NishimuraSeng et al. Sueoka et al. Saglam et al.

Recommended total cross section smaller than elastic only one!

Not all available experimental data reported… the picture would be too crowded!


Electron ionisationElectron ionisation

Semi-empirical model D. Emfietzoglou and M. Moscovitch, “Inelastic collision

characteristics of electrons in liquid water”, NIM B, vol. 193, pp. 71-78, 2002

Based on dielectric formalism for the valence shells (1b1, 3a1, 1b2 and 2a1) responsible for condensed-phase effects

Based on the binary encounter approximation for the K-shell (1a1)


Electron ionisation:Electron ionisation:total cross sectiontotal cross section

Different phases Geant4-DNA model:

liquid water Experimental data:

vapour

Plausible behaviour of Geant4 implementation

Phase differences appear more significant at lower energies

Geant4-DNA Born ionisation Itikawa & Mason ionisation (recommended)


Proton ionisationProton ionisation

Cross section based on two complementary models

a semi-empirical analytical approach with parameters specifically calculated for liquid water

for 100 eV < E < 500 keV

a model based on the Born theory

for 500 keV < E < 10 MeV

• M. Dingfelder et al., “Inelastic-collision cross sections of liquid water for interactions of energetic protons”, Radiat. Phys. Chem., vol. 59, pp. 255-275, 2000. • M. E. Rudd et al., “Cross sections for ionisation of water vapor by 7-4000 keV protons”, Phys. Rev. A, vol. 31, pp. 492-494, 1985.• M. E. Rudd et al., “Electron production in proton collisions: total cross sections”, Rev. Mod. Phys., vol. 57, no. 4, pp. 965-994, 1985.


Proton ionisation: Proton ionisation:

total cross sectiontotal cross sectionAll measurements performed by the same team

at different accelerators and time

Even data taken by the same group exhibit inconsistencies !

systematic is difficult to control in delicate experimental conditions

Geant4-DNA models look plausible

Hard to discuss phase effects in these experimental conditions!

Goodness-of-fit test Geant4 DNA model incompatible with

experimental data (p-value < 0.001)

Compatibility w.r.t. data fit? Cramer-von Mises test: p-value = 0.1 Anderson-Darling test: p-value <0.001

PNL data early Van de Graaff data late Van de Graaff data early Univ. Nebraska-Lincoln data late Univ. Nebraska-Lincoln data tandem Van de Graaff data

Geant4-DNA

Fit to experimental

data

M. E. Rudd, T. V. Goffe, R. D. DuBois, L. H. Toburen, “Cross sections for ionisation of water vapor by 7-4000 keV protons”, Phys. Rev. A, vol. 31, pp. 492-494, 1985.

Different phasesGeant4-DNA model: liquid waterExperimental data: vapour


Proton and hydrogen charge change Proton and hydrogen charge change

Cross section based on a semi-empirical approach Described by an analytical formula

With parameters optimised from experimental data in vapour

• M. Dingfelder et al., “Inelastic-collision cross sections of liquid water for interactions of energetic protons”, Radiat. Phys. Chem., vol. 59, pp. 255-275, 2000.• B. G. Lindsay et al., “Charge transfer of 0.5-, 1.5-, and 5-keV protons with H2O: absolute differential and integral cross sections”, Phys. Rev. A, vol. 55, no. 5, pp. 3945-3946, 1997.• R. Dagnac et al., “A study on the collision of hydrogen ions H+

1 , H+2 and H+

3 with a water-vapour target”, J. Phys. B, vol. 3, pp. 1239-1251, 1970.• L. H. Toburen et al., “Measurement of highenergy charge transfer cross sections for incident protons and atomic hydrogen in various gases”, Phys. Rev., vol. 171, no. 1, pp. 114-122, 1968


Charge change cross section: Charge change cross section: proton and hydrogenproton and hydrogen

Different phases Geant4-DNA model: liquid Experimental data: vapour

Goodness-of-fit test Geant4-DNA model experimental data (white symbols only)

Anderson-Darling test Cramer-von Mises test Kolmogorov-Smirnov test Kuiper test Watson test

p-value > 0.1 from all tests

… … but some data were used to but some data were used to optimise the semi-empirical optimise the semi-empirical

model!model!

Lindsay et al. Dagnac et al. Toburen et al. Berkner et al. Cable Koopman Chambers et al.

Large discrepancies

among the data!


Conclusion from Conclusion from comparisonscomparisonsGeant4-DNA models (liquid) look plausible when compared to available experimental data (vapour)

More experimental data are neededMore experimental data are needed In liquid water for simulation model validation

In vapour and ice to study the importance of phase effects in modelling particle interactions with the medium

With good control of systematiccontrol of systematic and reproducibilityreproducibility of experimental conditions!

Hard to draw firm conclusions about phase effects Available experimental data exhibit significant discrepancies in many cases

Some of these data have been already used to constrain or optimize semi-empirical models


Exploiting the toolkitExploiting the toolkitFor the first time

a general-purpose Monte Carlogeneral-purpose Monte Carlo system is equipped with functionality specific

to the simulation of biological effects of radiationbiological effects of radiation

Geant4-DNA physics processes User InterfaceKernel

Geometry Visualisation


ContextContextUnderstanding the health effects of low doses of ionizing radiation is the challenge of today’s radiobiology research

At the cell scale, recent results include the observation of bystander effects adaptive response gene expression changes genomic instability genetic susceptibility

► May question the validity of health risk estimation at low doses of radiation

► Consequences for radiotherapy, environment exposure, space exploration…

Dedicated worldwide experimental facilities to investigate the interaction of ionizing radiation with living cells radioactive sources classical beams microbeams: allow a perfect control of the deposited dose in the targeted cell

(e.g. the CENBG irradiation facility in France)


AIFIRA equipped with a cellular irradiation microbeam line

3 MeV proton or beam

single cell & single ion mode

Targeting accuracy on living cells in air: a few µm

Able to quantify DNA damages like double strand breaks

CENBG AIFIRA irradiation facility

in Bordeaux, France

© IPB/CENBG


Realistic cellular geometries Realistic cellular geometries from confocal microscopyfrom confocal microscopy

ability to control depth of fielddepth of field

elimination of background informationbackground information away from the focal plane

(that leads to image degradation)

collect serial optical sectionsoptical sections from thick specimens

© Olympus

Confocal microscopy offers several advantages over

conventional widefield optical microscopy


Confocal microscopyConfocal microscopyImages of human keratinocyte cells HaCaT/(GFP-H2B)Tg acquired at CENBG cell line used in single cell irradiation at CENBG

Cells fixed after 4 hours or 24 hours of incubation (cell irradiation conditions)

Staining Nucleus: Hoechst 33342 dye (DNA marker)

Cytoplasm: propidium iodide, (RNA and DNA marker).

Nucleoli (high chromatine and protein concentration regions): idem

Acquisition 2D images acquired every 163 nm with a Leica® DMR TCS SP2

confocal microscope

several 2D resolutions, up to 512 × 512 pixels

Image reconstruction 3D stacking using the Leica Confocal Software®

filtering and phantom geometry reconstruction with Mercury® Computer Systems, Inc. Amira® suite

© IPB/CENBG

© IPB/CENBG


Building cellular modelsBuilding cellular models

Selection of four “phantoms” reconstructed from 128×128 2D confocal images.

Incubation : 4 hours for cells a and b

24 hours for cells c and d

The cytoplasm and nucleoli appear in red while the nucleus is shown in blue

© IPB/CENBG

a b

c d


Geometry modellingGeometry modelling

Not available in ad-hoc

Monte Carlo codes

Exploit the advantage of a general purpose Monte Carlo system

Powerful Geant4 geometry packagePowerful Geant4 geometry package

Use of functionality already existing in Geant4

Voxel geometriesVoxel geometries +

Navigation optimisation techniquesNavigation optimisation techniques

Direct benefit from investment in the Geant4 toolkit

Realistic rendering of the biological systemsImportant for overall realistic simulation

results

Parameterised volumesNested parameterisation


Cellular phantoms in Cellular phantoms in Geant4Geant4

Implemented either as parameterised volumes or nested geometries

(faster navigation above 64x64 resolution)

Composition: liquid water (compatible with Geant4 DNA models)

These cellular models are publicly available in the Geant4 microbeammicrobeam Advanced Example geant4/examples/advanced/microbeam

011

1 2 3

011

1 2 31 2 3

4 5 …

1 2 3

4 5 …


2.37 MeV +

hitting the cell

Cellular phantom modelCellular phantom model

24h incubated cell

Irradiated with a 2.37 MeV + beam

64 x 64 x 60 resolution

0.36 x 0.36 x 0.16 µm3 voxel size

cytoplasm

nucleus~10 µm


Shower in cellular Shower in cellular phantomphantom

Ch

arg

e d

ecre

ase

Ch

arg

e in

cre

ase

Ela

sti

c s

catt

eri

ng

Excit

ati

on

Ion

isati

on

(unit: µm)

2.37 MeV + delivered on targeted cell by the CENBG microbeam irradiation facility

• G4 DNA processes• CPU ~45 min(preliminary timing)

ZOOM


Geant4 DNA capabilitiesGeant4 DNA capabilities

With this Geant4 extension, it is now possible to study the energy deposit distribution produced by a primary particle and its secondaries inside a cell

Access distributions in nucleus, cytoplasm, mitochondria…

What you get in return is more than your own investment!


Changing scaleChanging scaleLarge effort for microscopic modelling of interactions and biological systems in Geant4

Parallel approach: macroscopic modelling in Geant4

Concept of dose in a cell population

Statistical evaluation of radiation effects from empirical data

All this is possible in the same simulation environment (toolkit)

Human cell lines irradiated with X-rays

Courtesy E. Hall

Example: modelling cell survival fractioncell survival fraction

in a population of irradiated cells


ExampleExample Computation of dose in a cell population and estimation of survival fraction

Monolayer

V79-379A cells

Proton beam

E= 3.66 MeV/n

Linear-Quadratic model

Folkard et al., Int. J. Rad. Biol., 1996

α = 0.32β = -0.039

Macroscopic cell survival models to be distributed in Geant4 (advanced example in preparation)

Dose (Gy)

Continuous line:LQ theoretical model

with Folkard parameters

Data points:Geant4 simulation results

Su

rviv

al


ConclusionConclusionThe Geant4 DNA processes are publicly available

Can be applied to realistic cell geometries

Full comparison against vapour/ice will be published evaluation of phase effects

Thanks to the flexibility of policy-based code design of Geant4 DNA, any interaction model can be easily implemented in a few hours and automatically integrated in Geant4 !

Not limited to radiation biology…


PerspectivesPerspectivesShort term Geant4 DNA processes

will be publicly available in Geant4 9.1 on 14 December 2007

Microdosimetry advanced example will be available in the next Geant4 releases (presumably end of June 2008) illustrates how to use the Geant4 DNA physics processes

Cellular survival advanced example in preparation

Other physics models thanks to the novel software design

Longer term Chemical phase: production of radical species

Geometry-dedicated development cycle: DNA geometry modelling

Biological phase: prediction of DNA damages (double strand breaks – fatal lesions, DNA fragments…) after irrradiation

Other materials than liquid water: DNA bases, silicon etc.


For discussion…For discussion…

Geant4-DNA proposes a paradigm shift Open source, freely available software

Microdosimetry/radiobiology functionality in a general-purpose Monte Carlo code

Availability of multiple models in the same environment

Equal importance to functionality and software technology

Foster collaboration within the scientific community Theoretical modelling, experimental measurements, software technology

Promote feedback from users of the software

Comments and suggestions are welcome...


AcknowledgmentAcknowledgmentThanks to M. Dingfelder and D. Emfietzoglou for theoretical support

W. Friedland and H. Paretzke for fruitful discussions and suggestions

P. Nieminen for motivation and support to the project through ESA funding

COST-P9 for supporting short-term visits

R. Capra, Z. Francis, G. Montarou for preliminary contributions at an early stage

G. Cosmo and I. McLaren for support in the Geant4 system testing process

K. Amako for support in releasing the Geant4-DNA code documentation

Z. W. Bell (TNS Senior Editor) for his advice in the paper publication process

CERN Library for providing many reference papers

Thanks to Nigel Mason and CECAM for organizing this workshop and supporting our participation!

maria grazia pia, infn genova for microdosimetry for microdosimetry cecam workshop lyon, 3-6...

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