Proton irradiation of DNA nucleosides in the gas phase

The four DNA nucleosides guanosine, adenosine, cytidine and thymidine have been produced in the gas phase by a laser thermal desorption source, and irradiated by a beam of protons with 5 keV kinetic energy. The molecular ions as well as energetic neutrals formed have been analyzed by mass spectrometry in order to shed light on the ionization and fragmentation processes triggered by proton collision. A range of 8-20 eV has been estimated for the binding energy of the electron captured by the proton. Glycosidic bond cleavage between the base and sugar has been observed with a high probability for all nucleosides, resulting in predominantly intact base ions for guanosine, adenosine, and cytidine but not for thymidine where intact sugar ions are dominant. This behavior is influenced by the ionization energies of the nucleobases (G < A < C < T), which seems to determine the localization of the charge following the initial ionization. This charge transfer process can also be inferred from the production of protonated base ions, which have a similar dependence on the base ionization potential. Other dissociation pathways have also been identified, including further fragmentation of the base and sugar moieties for thymidine and guanosine, respectively, and partial breakup of the sugar ring without glycosidic bond cleavage mainly for adenosine and cytidine. These results show that charge localization following ionization by proton irradiation is important in determining dissociation pathways of isolated nucleosides, which could in turn influence direct radiation damage in DNA.

Inter- and Intrafraction Target Motion in Highly Focused Single Vocal Cord Irradiation of T1a Larynx Cancer Patients

PURPOSE: The purpose of this study was to verify clinical target volume-planning target volume (CTV-PTV) margins in single vocal cord irradiation (SVCI) of T1a larynx tumors and characterize inter- and intrafraction target motion.

METHODS AND MATERIALS: For 42 patients, a single vocal cord was irradiated using intensity modulated radiation therapy at a total dose of 58.1 Gy (16 fractions × 3.63 Gy). A daily cone beam computed tomography (CBCT) scan was performed to online correct the setup of the thyroid cartilage after patient positioning with in-room lasers (interfraction motion correction). To monitor intrafraction motion, CBCT scans were also acquired just after patient repositioning and after dose delivery. A mixed online-offline setup correction protocol ("O2 protocol") was designed to compensate for both inter- and intrafraction motion.

RESULTS: Observed interfraction, systematic (Σ), and random (σ) setup errors in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions were 0.9, 2.0, and 1.1 mm and 1.0, 1.6, and 1.0 mm, respectively. After correction of these errors, the following intrafraction movements derived from the CBCT acquired after dose delivery were: Σ = 0.4, 1.3, and 0.7 mm, and σ = 0.8, 1.4, and 0.8 mm. More than half of the patients showed a systematic non-zero intrafraction shift in target position, (ie, the mean intrafraction displacement over the treatment fractions was statistically significantly different from zero; P<.05). With the applied CTV-PTV margins (for most patients 3, 5, and 3 mm in LR, CC, and AP directions, respectively), the minimum CTV dose, estimated from the target displacements observed in the last CBCT, was at least 94% of the prescribed dose for all patients and more than 98% for most patients (37 of 42). The proposed O2 protocol could effectively reduce the systematic intrafraction errors observed after dose delivery to almost zero (Σ = 0.1, 0.2, 0.2 mm).

CONCLUSIONS: With adequate image guidance and CTV-PTV margins in LR, CC, and AP directions of 3, 5, and 3 mm, respectively, excellent target coverage in SVCI could be ensured.

In situ ATR-FTIR study of H2O and D2O adsorption on TiO2 under UV irradiation

The adsorption of water and deuterium oxide on TiO2 surfaces was investigated in the dark as well as under UV(A) irradiation using in situ ATR-FTIR spectroscopy under oxygen and oxygen free conditions. Adsorption of H2O-D2O mixtures revealed an isotopic exchange reaction occurring onto the surface of TiO2 in the dark. Under UV(A) irradiation, the amount of both OH and OD groups was found to be increased by the presence of molecular oxygen. Furthermore, the photocatalytic formation of hydroperoxide under oxygenated condition has been recorded utilizing Attenuated Total Reflection Fourier Transformed Infrared (ATR-FTIR) spectroscopy which appeared as new band at 3483 cm-1. Different possible mechanisms are discussed in terms of the source of hydroxyl groups formed and/or hydration water on the TiO2 surface for the photocatalytic reaction and photoinduced hydrophilicity.

The potential of electron beam irradiation for simultaneous surface modification and bioresorption control of PLLA for medical device applications

Bioresorbable polymers have been widely investigated as materials exhibiting significant potential for successful application in the medical fields of bone fixation devices and drug delivery. Further to the ability to control degradation, surface engineering of polymers has been highlighted as a key method central to their development. Previous work has demonstrated the ability of electron beam (e-beam) technology to control the degradation profiles and bioresorption of a number of commercially relevant bioresorbable polymers (poly-l-lactic acid (PLLA), L-lactide/ DL-lactide co-polymer (PLDL) and poly(lactic-co-glycolic acid) (PLGA). This work investigates the further potential of e-beam technology to impart added biofunctionality through the manipulation of polymer (PLLA) surface properties. A Dynamatron Continuous DC e-beam unit (Synergy Health, UK), with beam energies of 0.5, 0.75, and 1.5 MeV, was used for the irradiation of PLLA samples with delivered surface doses of 150 or 500 kGy at each energy level. The chosen conditions reflect the need to achieve a specific surface modification for the control of surface degradation as demonstrated in previous work. Surface characterization was then performed using contact angle analysis, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy.
Results demonstrated a significant increase in surface wettability post e-beam treatment. In correlation with this, XPS data showed the introduction of oxygen-containing functional groups to the surface of PLLA. Raman spectroscopy indicated chain scission in the near surface region of PLLA. E-beam irradiation did not seem to affect the surface roughness of PLLA as a direct consequence of the treatment. In conclusion electron beam surface modification has been found to modify both the surface-to-bulk bioresorption profile and the surface hydrophilicity. Both could provide benefits in relation to the performance of implantable medical devices.

Irradiation of bioresorbable biomaterials for controlled surface degradation

Bioresorbable polymers increasingly are the materials of choice for implantable orthopaedic fixation devices. Controlled degradation of these polymers is vital for preservation of mechanical properties during tissue repair and controlled release of incorporated agents such as osteoconductive or anti-microbial additives. The work outlined in this paper investigates the use of low energy electron beam irradiation to surface modify polyhydroxyacid samples incorporating beta tricalcium phosphate (β-TCP). This work uniquely demonstrates that surface modification of bioresorbable polymers through electron beam irradiation allows for the early release of incorporated agents such as bioactive additives. Samples were e-beam irradiated at an energy of 125 keV and doses of either 150 kGy or 500 kGy. Irradiated and non-irradiated samples were degraded in phosphate buffered saline (PBS), to simulate bioresorption, followed by characterisation. The results show that low energy e-beam irradiation enhances surface hydrolytic degradation in comparison to bulk and furthermore allows for earlier release of incorporated calcium via dissolution into the surrounding medium.

Influence of ultraviolet-B irradiation on engraftment, graft-versus-host disease and graft-versus-leukemia effect in a rat model for allogeneic bone marrow transplantation

Ultraviolet-B (UVB) irradiation is known to inhibit lymphocyte activity and consequently to reduce the incidence of graft-versus-host disease (GVHD) in experimental models for allogeneic bone marrow transplantation (BMT). GVHD is frequently associated with morbidity and mortality, but also with the beneficial graft-versus-leukemia (GVL) effect, demonstrated by a reduction in the incidence of leukemia relapse. In this study, we investigated whether UVB treatment of allogeneic T cells could prevent GVHD while sparing the beneficial GVL effect following allogeneic BMT in the Brown Norway myelocytic leukemia (BNML) rat model analogous to human acute myelocytic leukemia (AML). The dose of UVB required to abolish lethal GVHD in the rat allogeneic BMT model (WAG/Rij donors into BN recipients) was 4000 J/m2. However, this UVB dose simultaneously abrogated all GVL activity mediated by the T cells in the graft, while the radio-protective capacity of rat BM cells was strongly reduced. The number of allogeneic BM cells required to protect lethally irradiated BN rats was increased 50 to 100-fold. It is concluded that UVB acts as a non-selective form of T cell inactivation, and that UVB pretreatment of an allogeneic marrow graft is unlikely to be useful clinically as a preventive measure for GVHD, since other means of reduction of the number of functional T cells are less damaging to bone marrow stem cells.

Ultraviolet irradiation for the prevention of graft-versus-host disease and graft rejection in bone marrow transplantation

This review describes an approach to the prevention of graft-versus-host disease (GVHD) and graft rejection following allogeneic BMT that differs from conventional methods. Ultraviolet (UV) irradiation inhibits the proliferative responses of lymphoid cells to mitogens and alloantigens by inactivation of T lymphocytes and dendritic cells, and in animal models this can prevent both GVHD and graft rejection. It is important that the marrow repopulating capacity of haemopoietic stem cells is not damaged by the irradiation process. We have found that polymorphic microsatellite markers are a sensitive way of assessing the impact of UV irradiation on chimerism after BMT in rodents.

In-Situ, Simultaneous Irradiation and Monitoring of a Photocatalysed Organic Oxidation Reaction in a TiO2-coated NMR Tube

The semiconductor photocatalysed (SPC) oxidation of toluene is performed inside an NMR spectrometer and the reaction monitored simultaneously in-situ, using a fibre optic probe/diffuser to provide the UV light to activate the titania photocatalyst coating on the inside of the NMR tube. Such a system has great potential for the simple rapid screening of a wide range of SPC mediated organic reactions.

The application of a novel fluidised photo reactor under UV-Visible and natural solar irradiation in the photocatalytic generation of hydrogen

With advancements in the development of visible light responsive catalysts for H2 production frequently being reported, photocatalytic water splitting has become an attractive method as a potential ‘solar fuel generator’. The development of novel photo reactors which can enhance the potential of such catalyst, however, is rarely reported. This is particularly important as many reactor configurations are mass transport limited, which in term limits the efficiency of more effective photocatalysts in larger scale applications. This paper describes the performance of a novel fluidised photo reactor for the production of H2 over two catalysts under UV-Visible light and natural solar illumination. Catalysts Pt-C3N4 and NaTaO3.La were dispersed in the reactor and the rate of H2 was determined by GC-TCD analysis of the gas headspace. The unit was an annular reactor constructed from stainless steel 316 and quartz glass with a propeller located in the base to control fluidisation of powder catalysts. Reactor properties such as propeller rotational speed were found to enhance the photo activity of the system through the elimination of mass transport limitations and increasing light penetration. The optimum conditions for H2 evolution were found to be a propeller rotational speed of 1035 rpm and 144 W of UV-Visible irradiation, which produced a rate of 89 µmol h-1 g-1 over Pt-C3N4. Solar irradiation was provided by the George Ellery Hale Solar Telescope, located at the California Institute of Technology.

Assessment of DNA double-strand breaks induced by intravascular iodinated contrast media following in vitro irradiation and in vivo, during paediatric cardiac catheterization

Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X-ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess γH2AX-foci induction, which corresponded to the number of DNA double-strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double-strand breaks beyond that induced by radiation for ≥17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double-strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X-ray radiation investigations. 

Generation of overdense and high-energy electron-positron-pair plasmas by irradiation of a thin foil with two ultraintense lasers

A scheme for enhanced quantum electrodynamics (QED) production of electron-positron-pair plasmas is proposed that uses two ultraintense lasers irradiating a thin solid foil from opposite sides. In the scheme, under a proper matching condition, in addition to the skin-depth emission of gamma-ray photons and Breit-Wheeler creation of pairs on each side of the foil, a large number of high-energy electrons and photons from one side can propagate through it and interact with the laser on the other side, leading to much enhanced gamma-ray emission and pair production. More importantly, the created pairs can be collected later and confined to the center by opposite laser radiation pressures when the foil becomes transparent, resulting in the formation of unprecedentedly overdense and high-energy pair plasmas. Two-dimensional QED particle-in-cell simulations show that electron-positron-pair plasmas with overcritical density 10(22) cm(-3) and a high energy of 100s of MeV are obtained with 10 PW lasers at intensities 10(23) W/cm(2), which are of key significance for laboratory astrophysics studies.

Dynamics and structure of self-generated magnetics fields on solids following high contrast, high intensity laser irradiation

The dynamics of self-generated magnetic B-fields produced following the interaction of a high contrast, high intensity (I > 10¹⁹W cm^-2) laser beam with thin (3 μm thick) solid (Al or Au) targets is investigated experimentally and numerically. Two main sources drive the growth of B-fields on the target surfaces. B-fields are first driven by laser-generated hot electron currents that relax over ∼10-20 ps. Over longer timescales, the hydrodynamic expansion of the bulk of the target into vacuum also generates B-field induced by non-collinear gradients of density and temperature. The laser irradiation of the target front side strongly localizes the energy deposition at the target front, in contrast to the target rear side, which is heated by fast electrons over a much larger area. This induces an asymmetry in the hydrodynamic expansion between the front and rear target surfaces, and consequently the associated B-fields are found strongly asymmetric. The sole long-lasting (>30 ps) B-fields are the ones growing on the target front surface, where they remain of extremely high strength (∼8-10 MG). These B-fields have been recently put by us in practical use for focusing laser-accelerated protons [B. Albertazzi et al., Rev. Sci. Instrum. 86, 043502 (2015)]; here we analyze in detail their dynamics and structure.