1. Nigel Mason Nigel Mason The Open University The Atomic and Molecular Database for Radiation Damage – How COST Nano - IBCT can help

2. What is the current status of the field of radiation damge ? Our studies in the mechanisms of radiation damage has developed rapidly in the last decade. Our studies in the mechanisms of radiation damage has developed rapidly in the last decade. For example role of DEA in DNA damage For example role of DEA in DNA damage

3. What is the current status of the field of radiation damge ? Development of new cancer therapies eg carbon ions.

4. HENCE Recent research has stressed the need to understand radiation damage at the molecular level This was aim of RADAM action 2003- 2008 Recent research has stressed the need to understand radiation damage at the molecular level This was aim of RADAM action 2003- 2008

5. This has been coupled with the need to understand effects of low dose long term exposure (EU RISCRAD programme) This has been coupled with the need to understand effects of low dose long term exposure (EU RISCRAD programme)

6. Three Grand Challenges 1. Understanding fundamental interactions between different types of radiation and biomolecule 2. Study of damage to DNA and other macromolecules in the cell 3. Developing models of such damage for use in therapy etc.

7. Radiation Damage – the mechanism What we need to understand is the mechanisms by which strand breaks in DNA occur. What we need to understand is the mechanisms by which strand breaks in DNA occur. Can this be understood by single collisions ? Can this be understood by single collisions ? Is the damage located at specific sites in the DNA chain ? Is the damage located at specific sites in the DNA chain ? Can we ‘control’ the site & amount of damage ? Can we ‘control’ the site & amount of damage ?

8.  or X e-e- < 20 eV Single and double strand breaks may be induced by secondary species: a large number of secondary electron with kinetic energies below about 20 eV, are produced along the radiation track Damage of the genome in living cell by ionising radiation is about 1/3 a direct and 2/3 an indirect processes. Radiation damage to DNA Electron induced damage of DNA

9. V(R) 0 A + B + e - A - + B R D(A-B) EA(A) e - + AB → (AB) - * Transit negative ion (TNI) → AB - → AB + e - → A - + B autodetachment molecular anion dissociative electron attachment Dissociative Electron Attachment

10. Thymine + e - → TNI - * → electron attachment C5H6N2O2-C5H6N2O2- e-e- dissociative electron attachment (T-H) - + H (T-2H) - + neutral(s) C 4 H 5 N 2 O - + neutral(s) C 2 H 3 N 2 O - + neutral(s) C 3 H 2 NO - + neutral(s) CN - + neutral(s) O - + neutral(s) H - + neutral(s) OCN - + neutral(s) → → → → → → C 3 H 4 N - + neutral(s) → → → → DEA to biomolecules 126 amu 125 amu 124 amu 1 amu 16 amu 26 amu 42 amu 54 amu 68 amu 99 amu 73 amu

11. 01234 0 2 4 6 8 10 12 Cross section (10 -20 m 2 ) Electron energy (eV) H loss e-e- DEA in Thymine (M-H) - 125 amu

12. Site selectivity and Chemical control Such site selectivity appears to be maintained in larger biomolecules Eg if add sugar to base (thymidine) can still target thymine site So DEA indicates radiation damage can be explained at a molecular level

13. DEA and radiosensitizers Can we exploit such site specific damage ? Eg in developing new cancer therapies ? Consider radiosensitizers Au nanoparticles

14. E.g exploit enhanced DEA to develop new radiosensitizers 5-nitrouracil

15. So exploit enhanced DEA to develop new radiosensitizers 5-nitrouracil

16. SO !!! We are now developing a picture of radiation damage that is based on fundamental collision physics Such an understanding may/is leading to opportunity for controlling damage pathways Exploitation for new radiotherapy techniques ?

17. But are we asking the right questions ?

18. We need to provide data that is useful in setting clinical protocols Medical applications require accurate dose evaluation performed using models Available simulation codes (MCNPX, PARTRAC, PENELOPE, GEANT-4): Based on high-energy particle approximations, few molecular details are included

19. Energy degradation of electrons in H 2 O Energy scale (eV) H 2 O, 200 Torr 5 mm 2 keV incident energy (5 single tracks)

20. Different types of interactions 2 keV electrons in H 2 O Pressure: 200 Torr 5 single tracks Ionisation Neutral dissociation Excitation Auger

21. Such models need Cross sections !!!! Real numbers not just phenomenology !

22. Database assessment --What data is needed ? Electron impact processes Energy resolved cross sections Dissociation/ionisation processes Ion molecule interactions Charge state Energy dependence Fragmentation – branching ratios Photon interactions X-ray to UV Spectroscopy – photostability

23. Data providers * theory * experiment Data users in various application fields * fusion science * astrophysics * industrial plasmas * environmental physics * medical (radiotherapy) etc. Data centers data compilation data evaluation (important but not easy) dissemination and updating of database retrievable online database = easy to access, use, find data Data requests Data needs Data provide Data search Data requested Data search for check International A&M data center network IAEA, NIFS, A-PAN, KAERI, NIST, ORNL, GAPHIOR, VAMDC, Data provided feedback Views from Database assessed data on cross sections

24. Electron interactions data in H 2 O

25. Summary of the Recommended data on the electron collision cross section for H 2 O Y. Itikawa and N.J.Mason, J. Phys. Chem. Ref. Data 34 (2005)1

26. Total electron scattering and ionisation cross sections in H 2 O Total Ionisation 100% Discrepancy below 5eV *Muñoz et al., Phys. Rev. A (2007)

27. e-H 2 O integral cross section data (Courtesy of G Garcia) Total scattering (5%) Integral elastic and inelastic (10%) Ionisation (7%) Excitation (15%) Neutral dissociation (15%)

28. Elastic scattering - H 2 O Cho, Park, Tanaka, Buckman JPB 37 625 (2004)

29. But what is the measurable in clinic ?

30. The stopping power: (-dE/dx)

31. Mass stopping power of electrons in water: -dE/  dx (Munoz et al)

32. But such complete data sets are rare For most biomoleules MOST cross sections are missing Some may be calculated – eg ionisation (Theory – Kim (BE) and Deutsch Maerk ) And compare well with experiments (But note kinetic effects in products) Or for total, elastic, some excitations Quantemol package (J Tennyson)

33. But…. To date most of the ideas are based on knowledge in gas phase The cell is not a gas !! For example electronic states are shifted ! So are gas phase cross sections relevant in modelling radiation damage in a cell ?

34. Water ice Note : Blue shift in the solid phase

35. Carbon dioxide Note : Blue shift in the solid phase

36. Comparison of gas and solid phase Methylamine Note absence of low lying bands in solid phase

37. Cross sections in condensed phase TRK sum rule still holds !! So where does ’lost flux’ go ? How to measure cross sections in condensed phase ?

38. Studies in condensed phase Evidence is that same site selectivity etc holds in condensed films

39. GCAT G+C+A+T EA - electron affinity EA(CN)= 3.82 eV EA(CNO)= 3.61 eV DEA to oligomers O P O-O- NH 2 N N N N HO O O O NH 2 O N N P O O O O-O- O O N N N N N N O O O O O O O-O- O OH G C A T oligomer tetramer (1172 amu) P CN - CNO - Gas phase Condensed phase

40. Studies in condensed phase Evidence is that same site selectivity etc holds in condensed films Cross sections in ice have been defined (Sanche)

41. But a cell is not a solid either ! So what is the best mimic of the environment of biomolecules in a cell ? What can be explored in the Lab ?

42. Experiments with clusters Groningen University T Schladtholter et al) Ion irradiation of biomolecular clusters Eg C + on nucleobases Deoxyribose and amino acids Uracil and Thymine Different fragmentation patterns

43. Experiments with clusters Experiments in He droplets (Innsbruck) But is this a mimic of ‘real conditions’ ?

44. But what about other biomolecules ? DNA is not the only target in the cell !!! What about other molecules ?

45. What is the role of water and proteins in electron induced damage of DNA? DNA Proteins (amino acids) M. Begusova et al., Int. J.Radiat.Biol. (2003) bases sugar undamage atoms proteins undamage atoms DNA proteins Free electron attachment to amino- acids/nucleobases complexes radiation damage of proteins radiation

46. What is the effect of damage to the cell membrane ? radiation damage of proteins

47. But what about other biomolecules ? How do we study Lipids and proteins ? In gas phase or on surfaces ? Damage may change ion transport through cell membrane !

48. Direct damage vs Indirect All of the discussion so far is based on direct damage but this is only 1/3 of the damage ! What about mechanisms of indirect damage ?

49. And no description can ignore repair So in reality we are only exploring one part (important though it is) of the radiation damage process

50. And we have more to explore with new projectiles What about damage induced by positrons ?? How do positrons damage DNA ? Role of annihilation and gamma rays ?

51. So lots of data needed ! How do we co-ordinate data collection ? Where does the user find it ? When collected how/where is it stored and ‘ratified’ ?

52. VAMDC is funded under the “Combination of Collaborative Projects and Coordination and Support Actions” Funding Scheme of The Seventh Framework Program. Call topic: INFRA-2008-1.2.2 Scientific Data Infrastructure. Grant Agreement number: 239108.

53. VAMDC will provide a scientific data e-infrastructure enabling easy access to A+M resources Http://www.vamdc.org/

54. Atomic & Molecular data underpins a wide range of basic and applied research and industrial development Thus there is a need to collect, assess and allow access to a wide range of A&M data Hence there many A&M related DATABASES have been developed but such databases are…. Often in different formats Access maybe restricted or ‘regional’ Often fragmentary providing ‘partial resource’ So need a common portal ‘single point entry’ to access multiple databases for comprehensive data mining.

55. KEY VAMDC OUTCOMES Develop or/and extend standards for interoperability of AM resources Implementation of selected databases / Compatibility with existing extraction tools Find resources easily  Registries at a fine granularity Query those resources  Query protocols or/and languages Transfer large quantities of data, Asynchronous Queries Create a safe environment where latest AM data can be easily published (even small sets)‏ Linking producers and users KEY BENEFITS to using VAMDC Find any type of A&M data with a “click” Uniform access, i.e. saving time with format of data, tools development Allows cross-matching of different sets of A & M data Allows wide access to the latest published AM data This then allows Increased level of scientific analysis

56. VAMDC must meet the users requirements but also the producers requirements VAMDC must be built in collaboration with many A&M specialists

57. A&M users (and data providers) VAMDC has, in its first year, sought to engage with its ultimate user base through meetings and workshops and this session reviews some of those links

58. A & M Users – VAMDC clientele – Astrophysics/Astronomy/Planetary Science – Atmospheric Science – Fusion – Plasma Science – Radiation science

59. Astronomy/ Planetary Science Main providers of VAMDC project Data to interpret observations and develop models Many databases exist and are in VAMDC

60. Astronomy/ Planetary Science A&M Data needs increase with: New projects e.g. ALMA Developing science (e.g. exoplanet atmospheres)

61. Planetary Science Recent examples of A&M data Titan atmosphere Surfaces of Saturnian moons Physical and Chemistry of KBOs Need ice spectra - Ghosst

62. Linking to other EU projects Europlanet/ IDIS project Lassie (Training Network) COST Chemical Cosmos Helio Great (Training Network)

63. Atmospheric Science One of worlds largest and most controversial fields of science Global Warming – Climate Change Pollution and health – legislation Major observational programme – Remote sensing

64. Atmospheric Science Global Warming – Molecular spectra Photoabsorption cross sections Pollution/ aerosols – Chemical reactions Remote sensing - IR and UV spectra Instrumentation – Analytical tools for legislation

65. Atmospheric Science Well provide with databases HITRAN Integrate VAMDC & Hitran UV/Vis+ Spectra Data Base

66. Fusion Science ITER one of the worlds largest science projects A&M central to its engineering IAEA have supported A&M databases for decades

67. Fusion Science IAEA AMDIS ALADDDIN database A&M data and particle surface interactions E.g. To design negative ion sources

68. Plasma Science Industrial development Device fabrication, pollution control, lighting, medicine A&M data need in plasma simulations Plasimo and Quantemol-D

69. The ideal of a virtual factory

70. Plasma science A&M data needed for modelling New feed gases for ‘greener’ world Nanotechnology = atomic/molecular scale Cross sections/rate constants needed VAMDC support for Workshops on plasma processing and lighting ESCAMPIG July 2010

71. Radiation damage Development of next generation therapy and understanding risk (e.g. effect of low dose but long term exposures – topical with Japan!)

72. Radiation damage Uses simulation codes (MCNPX, PARTRAC, PENELOPE, GEANT-4) Requires A & M data input (G Garcia presentation)

73. Radiation damage A&M data needed for track modelling Biological material is represented by gases (Tissue equivalent material) Setting protocols so need approved datasets Solid state/liquid cross sections needed VAMDC support for Workshop June 30-July 3, 2010 led to; Special volume being published New Cost Action will include working group data assembly and Recommendations – link to fusion/Euratom programme

74. VAMDC therefore has to Engage with users and providers Disseminate its product Sustain itself Then….

75. VAMDC has the potential to be the tool of primary choice for users of A&M data worldwide To be the ‘google’ for A&M