A technical study to economize the amount of zinc used in the production of radiogallium

Abstract For the production of radiogallium, the targets were prepared in two forms, namely, electroplated metal and pressed oxide. The target holder was selected from Cu-metal as a circular disk. The experimental yields of 66,67,68Ga produced from both irradiated natZnO and zinc metal targets are given and compared with the estimated yields as well as with the previously reported values. The ZnO target developed in this work appears to be more convenient and economical for local production of short-lived radiogallium, e.g. 66Ga and 68Ga.</jats:p

New activation cross section data on longer lived radio-nuclei produced in proton induced nuclear reaction on zirconium.

In the frame of a systematic study of charged particle production routes of medically relevant radionuclei, the exci- tation function for indirect production of 178mTa through natHf(α,xn)178−178mTa nuclear reaction was measured for the first time up to 40 MeV. In parallel, the side reactions natHf(α,x)179,177,176,175W, 183,182,178g,177,176,175Ta, 179m,177m,175Hf were also assessed. Stacked foil irradiation technique and γ-ray spectrometry were used. New experimental cross section data for the natTa(d,xn)178W reaction are also reported up to 40 MeV. The measured excitation functions are compared with the results of the ALICE-IPPE, and EMPIRE nuclear reaction model codes and with the TALYS 1.4 based data in the TENDL-2013 library. The thick target yields were deduced and compared with yields of other charged particle ((p,4n), (d,5n) and (3He,x)) production routes for 178W

Proton induced nuclear reactions on natural antimony up to 17 MeV

The activation cross sections of proton induced reactions on natSb target leading to the formation of the radioisotopes 121m,g,123mTe were measured. The experimental excitation functions were compared with the theoretical model calculations using the codes EMPIRE-3.1 and TALYS-1.4. The integral yields of the three radionuclides were calculated and the possibility of their production is discussed

Excitation functions of 3He-particle-induced nuclear reactions on 103Rh: Experimental and theoretical investigations

Excitation functions for the 3He-induced reactions on 103Rh as alternative pathway for the production of the medically used 103Pd were studied by the stacked foil technique. Excitation functions of the 103Rh(3α, x) 103Pd, 103,104,104m,105Ag and 100,101,101m,102,102mRh reactions were determined up to 27 MeV by detecting only the characteristic γ-rays obtained from the decay of residual nuclei. The experimental results were compared with the theoretical ones obtained from the EMPIRE-3.2 code and ‎the TENDL nuclear data library. From the measured cross-section data integral production yields were calculated

Accelerated radiation damage test facility using a 5 MV tandem ion accelerator

We have developed a new irradiation facility that allows to perform accelerated damage tests of nuclear reactor materials at temperatures up to 400�C using the intense proton (&lt;100 μA) and heavy ion (≈10 μA) beams produced by a 5 MV tandem ion accelerator. The dedicated beam line for radiation damage studies comprises: (1) beam diagnosis and focusing optical components, (2) a scanning and slit system that allows uniform irradiation of a sample area of 0.5-6 cm 2 , and (3) a sample stage designed to be able to monitor in-situ the sample temperature, current deposited on the sample, and the gamma spectrum of potential radio-active nuclides produced during the sample irradiation. The beam line capabilities have been tested by irradiating a 20Cr-25Ni-Nb stabilised stainless steel with a 3 MeV proton beam to a dose level of 3 dpa. The irradiation temperature was 356�C, with a maximum range in temperature values of �6�C within the first 24 h of continuous irradiation. The sample stage is connected to ground through an electrometer to measure accurately the charge deposited on the sample. The charge can be integrated in hardware during irradiation, and this methodology removes uncertainties due to fluctuations in beam current. The measured gamma spectrum allowed the identification of the main radioactive nuclides produced during the proton bombardment from the lifetimes and gamma emissions. This dedicated radiation damage beam line is hosted by the Dalton Cumbrian Facility of the University of Manchester

Etude de l'assemblage et de l'activation de la NADPH oxydase de phagocyte au niveau des membranes cellulaires

Neutrophils are phagocytic cells that destroy pathogens invading the human body through a massive production of reactive oxygen species (ROS) in an intracellular compartment: the phagosome. The precursor of these ROS, superoxide anion, is produced by the NADPH oxidase, a protein complex formed at the phagosomal membrane. The enzyme can also be localized in the plasma membrane and produce ROS in the extracellular space. An overproduction of ROS can then be responsible for pathological inflammations whereas an absence or a non-functional NADPH oxidase causes a serious disease named Chronic-granulomatous disease (CGD). Patients with CGD develop recurrent and severe infections. Some pathogens are able to escape destruction in the phagosome by, for example, modifying the phagosomal membrane composition or targeting the NADPH oxidase. NADPH oxidase is finely regulated in space and time. It consists of six subunits: two membrane proteins (NOX2 and p22ᵖᵸᵒˣ) constituting the catalytic center and four cytosolic proteins (p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ, p40ᵖᵸᵒˣ and Rac). The activation of NOX2 is based on the assembly of cytosolic proteins with membrane proteins. This assembly is done on the one hand by interactions between proteins and on the other hand by interactions with phospholipids. The aim of my thesis was to study the protein-lipid interactions that are involved in the activation of NOX2. A chimeric fusion protein called "Trimera" was the main tool in this work. It is composed of the p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ and Rac1 essential domains for the activation of the enzyme. Three variants of the prototype trimera were used, the p47 ∆PX, Rac1 PB2 and Rac1 PB6Q mutant trimeras. The mutations were created to study the involvement of the two lipid interaction domains, PX (Phox Homology) of p47ᵖᵸᵒˣ and the polybasic domain (PB) of Rac1, in NOX2 activation. Following in vitro measurements of superoxide anion production by NADPH oxidase and the determination of the affinity of the trimeras towards neutrophil membrane proteins, completed by in cellulo activity measurements, we have shown an important role of the PB domain of Rac1 for the formation of the complex but also for its activity while the PX domain is mainly important for its assembly in vitro. In the second part of my thesis, the study focused on the attachment of the trimer to membranes using a biomimetic system: liposomes of different phospholipid compositions and the myeloid cell line (PLB-985) differentiable into phagocytic cells. The interactions between the trimeras and the membranes were detected by confocal fluorescence microscopy but also by the biolayer-interferometry technique. These experiments showed that the prototype binds very efficiently to liposomes containing anionic phospholipids as well as to the plasma and phagosomal membrane of these phagocytic cells. The PX domain was shown to be very important for the binding of the trimera to these liposomes while the PB domain was shown again to be necessary for an efficient binding to the plasma and phagosomal membranes of PLB-985 cells. In conclusion, these studies have shown an important role of protein-lipid interactions for the maintenance of the complex but also a fine regulation of the complex formation according to the phospholipid composition, which needs to be better defined. This knowledge could be useful for a finely tuned regulation of the production of superoxide anion by the phagocyte NADPH oxidase.Les neutrophiles, cellules phagocytaires, détruisent les pathogènes envahissant le corps humain grâce à une production massive d'espèces réactives de l'oxygène (ERO ou FRO) dans un compartiment intracellulaire : le phagosome. Le précurseur de ces ERO, l'anion superoxyde est produit par la NADPH oxydase un complexe protéique formé à la membrane phagosomale. L'enzyme peut également être localisée dans la membrane plasmique et produit alors des ERO dans l'espace extracellulaire. Une surproduction d'ERO peut alors être responsable d'inflammations pathologiques alors que l'absence de NADPH oxydase est à l'origine d'une maladie grave, la granulomatose septique chronique (CGD) où les patients développent des infections récurrentes car ils sont incapables de détruire les pathogènes. Certains pathogènes peuvent aussi échapper à cette destruction en modifiant la membrane des phagosomes. La NADPH oxydase est finement régulée dans l'espace et le temps. Elle est constituée de six sous-unités : deux protéines membranaires (Nox2 et p22ᵖᵸᵒˣ) constituant le centre catalytique et quatre protéines cytosoliques (p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ, p40ᵖᵸᵒˣ et Rac). L'activation de Nox2 est basée sur l'assemblage des protéines cytosoliques avec les protéines membranaires. Cet assemblage se fait d'un part par des interactions entre les protéines et d'autre part, par des interactions avec les phospholipides. Le but de ma thèse a été d'étudier les interactions protéine-lipide qui se mettent en jeu afin d'activer Nox2. Une protéine de fusion chimérique appelée "Trimère " a été l'outil principal dans ce travail. Il est composé des domaines de p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ et Rac1 indispensable à l'activation de l'enzyme. Trois variants du trimère prototype ont été utilisés, les trimères mutants p47 ∆PX, Rac1 PB2 et Rac1 PB6Q. Les mutations ont été créés afin d'étudier l'implication des deux domaines d'interactions avec les lipides, PX de p47ᵖᵸᵒˣ et PB de Rac1 dans l'activation de Nox2. Suite à des mesures in vitro de production d'anion superoxyde par la NADPH oxydase et la détermination de l'affinité des trimères vis-à-vis des protéines membranaires de neutrophiles, complété par des mesures d'activité in cellulo, nous avons montré un rôle important du domaine PB de Rac1 pour la formation du complexe mais aussi pour son activité alors que le domaine PX est surtout important pour son assemblage in vitro. Dans la deuxième partie de ma thèse, l'étude s'est portée sur la fixation du trimère aux membranes en utilisant un système biomimétique : des liposomes de différentes compositions en phospholipides ainsi que la lignée de cellules myéloïde (PLB-985) différenciable en cellules phagocytaires. Les interactions entre les trimères et les membranes ont été détectés par microscopie confocale de fluorescence mais aussi par la technique de bio-layer-interférométrie. Ces expériences ont montré que le prototype se fixe très efficacement sur des liposomes contenant des phospholipides anioniques ainsi que sur la membrane plasmique et phagosomale de ces cellules phagocytaires. Le domaine PX s'est révélé très important pour la fixation du trimère sur ces liposomes alors que le domaine PB s'est montré de nouveau nécessaire pour une bonne fixation aux membranes plasmique et phagosomale des cellules PLB-985. Pour conclure, ces études ont montré un rôle important des interactions protéines-lipides pour le maintien du complexe mais aussi une régulation fine de la formation du complexe en fonction de la composition en phospholipides, qui demande à être mieux définie. Cette connaissance pourrait être utile pour contrôler la production d'anion superoxyde par la NADPH oxydase de phagocyte

Study of the assembly and activation of phagocyte NADPH oxidase in cellulo and in vitro

Les neutrophiles, cellules phagocytaires, détruisent les pathogènes envahissant le corps humain grâce à une production massive d'espèces réactives de l'oxygène (ERO ou FRO) dans un compartiment intracellulaire : le phagosome. Le précurseur de ces ERO, l'anion superoxyde est produit par la NADPH oxydase un complexe protéique formé à la membrane phagosomale. L'enzyme peut également être localisée dans la membrane plasmique et produit alors des ERO dans l'espace extracellulaire. Une surproduction d'ERO peut alors être responsable d'inflammations pathologiques alors que l'absence de NADPH oxydase est à l'origine d'une maladie grave, la granulomatose septique chronique (CGD) où les patients développent des infections récurrentes car ils sont incapables de détruire les pathogènes. Certains pathogènes peuvent aussi échapper à cette destruction en modifiant la membrane des phagosomes. La NADPH oxydase est finement régulée dans l'espace et le temps. Elle est constituée de six sous-unités : deux protéines membranaires (Nox2 et p22ᵖᵸᵒˣ) constituant le centre catalytique et quatre protéines cytosoliques (p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ, p40ᵖᵸᵒˣ et Rac). L'activation de Nox2 est basée sur l'assemblage des protéines cytosoliques avec les protéines membranaires. Cet assemblage se fait d'un part par des interactions entre les protéines et d'autre part, par des interactions avec les phospholipides. Le but de ma thèse a été d'étudier les interactions protéine-lipide qui se mettent en jeu afin d'activer Nox2. Une protéine de fusion chimérique appelée "Trimère " a été l'outil principal dans ce travail. Il est composé des domaines de p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ et Rac1 indispensable à l'activation de l'enzyme. Trois variants du trimère prototype ont été utilisés, les trimères mutants p47 ∆PX, Rac1 PB2 et Rac1 PB6Q. Les mutations ont été créés afin d'étudier l'implication des deux domaines d'interactions avec les lipides, PX de p47ᵖᵸᵒˣ et PB de Rac1 dans l'activation de Nox2. Suite à des mesures in vitro de production d'anion superoxyde par la NADPH oxydase et la détermination de l'affinité des trimères vis-à-vis des protéines membranaires de neutrophiles, complété par des mesures d'activité in cellulo, nous avons montré un rôle important du domaine PB de Rac1 pour la formation du complexe mais aussi pour son activité alors que le domaine PX est surtout important pour son assemblage in vitro. Dans la deuxième partie de ma thèse, l'étude s'est portée sur la fixation du trimère aux membranes en utilisant un système biomimétique : des liposomes de différentes compositions en phospholipides ainsi que la lignée de cellules myéloïde (PLB-985) différenciable en cellules phagocytaires. Les interactions entre les trimères et les membranes ont été détectés par microscopie confocale de fluorescence mais aussi par la technique de bio-layer-interférométrie. Ces expériences ont montré que le prototype se fixe très efficacement sur des liposomes contenant des phospholipides anioniques ainsi que sur la membrane plasmique et phagosomale de ces cellules phagocytaires. Le domaine PX s'est révélé très important pour la fixation du trimère sur ces liposomes alors que le domaine PB s'est montré de nouveau nécessaire pour une bonne fixation aux membranes plasmique et phagosomale des cellules PLB-985. Pour conclure, ces études ont montré un rôle important des interactions protéines-lipides pour le maintien du complexe mais aussi une régulation fine de la formation du complexe en fonction de la composition en phospholipides, qui demande à être mieux définie. Cette connaissance pourrait être utile pour contrôler la production d'anion superoxyde par la NADPH oxydase de phagocyte.Neutrophils are phagocytic cells that destroy pathogens invading the human body through a massive production of reactive oxygen species (ROS) in an intracellular compartment: the phagosome. The precursor of these ROS, superoxide anion, is produced by the NADPH oxidase, a protein complex formed at the phagosomal membrane. The enzyme can also be localized in the plasma membrane and produce ROS in the extracellular space. An overproduction of ROS can then be responsible for pathological inflammations whereas an absence or a non-functional NADPH oxidase causes a serious disease named Chronic-granulomatous disease (CGD). Patients with CGD develop recurrent and severe infections. Some pathogens are able to escape destruction in the phagosome by, for example, modifying the phagosomal membrane composition or targeting the NADPH oxidase. NADPH oxidase is finely regulated in space and time. It consists of six subunits: two membrane proteins (NOX2 and p22ᵖᵸᵒˣ) constituting the catalytic center and four cytosolic proteins (p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ, p40ᵖᵸᵒˣ and Rac). The activation of NOX2 is based on the assembly of cytosolic proteins with membrane proteins. This assembly is done on the one hand by interactions between proteins and on the other hand by interactions with phospholipids. The aim of my thesis was to study the protein-lipid interactions that are involved in the activation of NOX2. A chimeric fusion protein called "Trimera" was the main tool in this work. It is composed of the p67ᵖᵸᵒˣ, p47ᵖᵸᵒˣ and Rac1 essential domains for the activation of the enzyme. Three variants of the prototype trimera were used, the p47 ∆PX, Rac1 PB2 and Rac1 PB6Q mutant trimeras. The mutations were created to study the involvement of the two lipid interaction domains, PX (Phox Homology) of p47ᵖᵸᵒˣ and the polybasic domain (PB) of Rac1, in NOX2 activation. Following in vitro measurements of superoxide anion production by NADPH oxidase and the determination of the affinity of the trimeras towards neutrophil membrane proteins, completed by in cellulo activity measurements, we have shown an important role of the PB domain of Rac1 for the formation of the complex but also for its activity while the PX domain is mainly important for its assembly in vitro. In the second part of my thesis, the study focused on the attachment of the trimer to membranes using a biomimetic system: liposomes of different phospholipid compositions and the myeloid cell line (PLB-985) differentiable into phagocytic cells. The interactions between the trimeras and the membranes were detected by confocal fluorescence microscopy but also by the biolayer-interferometry technique. These experiments showed that the prototype binds very efficiently to liposomes containing anionic phospholipids as well as to the plasma and phagosomal membrane of these phagocytic cells. The PX domain was shown to be very important for the binding of the trimera to these liposomes while the PB domain was shown again to be necessary for an efficient binding to the plasma and phagosomal membranes of PLB-985 cells. In conclusion, these studies have shown an important role of protein-lipid interactions for the maintenance of the complex but also a fine regulation of the complex formation according to the phospholipid composition, which needs to be better defined. This knowledge could be useful for a finely tuned regulation of the production of superoxide anion by the phagocyte NADPH oxidase

Cross sections and isomeric cross-section ratios in the interactions of fast neutrons with isotopes of mercury

Excitation functions were measured for the reactions Hg-196(n, 2n)Hg-195(m,g),Hg-198(n, 2n)Hg-197(m,g),Hg-204(n, 2n)Hg-203,Hg-198(n,p)Au-198(g), and Hg-199(n,p)Au-199 over the neutron energy range of 7.6-12.5 MeV. Quasimonoenergetic neutrons were produced via the H-2(d,n)He-3 reaction using a deuterium gas target at the Julich variable energy compact cyclotron CV 28. Use was made of the activation technique in combination with high-resolution, high-purity Ge detector gamma-ray spectroscopy. All the data were measured for the first time over the investigated energy range. The transition from the present low-energy data to the literature data around 14 MeV is generally good. Nuclear model calculations using the codes STAPRE and EMPIRE-2.19, which employ the statistical and precompound model formalisms, were undertaken to describe the formation of both the isomeric and ground states of the products. The total reaction cross section of a particular channel is reproduced fairly well by the model calculations, with STAPRE giving slightly better results. Regarding the isomeric cross sections, the agreement between the experiment and theory is only in approximate terms. A description of the isomeric cross-section ratio by the model was possible only with a very low value of eta, i.e., the Theta(eff)/Theta(rig) ratio

Excitation functions of proton-induced reactions on natFe and enriched 57Fe with particular reference to production of 57Co

Excitation functions of the reactions (nat)Fe(p,xn)(55,56,57,58)Co, (nat)Fe(p,x)(51)Cr, (nat)Fe(p,x)(54)Mn, (57)Fe(p,n)(57)Co and (57)Fe(p,alpha)(54)Mn were measured from their respective thresholds up to 18.5MeV, with particular emphasis on data for the production of the radionuclide (57)Co (T(1/2)=271.8d). The conventional stacked-foil technique was used, and the samples for irradiation were prepared by an electroplating or sedimentation process. The measured excitation curves were compared with the data available in the literature as well as with results of nuclear model calculations. From the experimental data, the theoretical yields of the investigated radionuclides were calculated as a function of the proton energy. Over the energy range E(p)=15-->5MeV the calculated yield of (57)Co from the (57)Fe(p,n)(57)Co process amounts to 1.2MBq/microAh and from the (nat)Fe(p,xn)(57)Co reaction to 0.025MBq/microAh. The radionuclidic impurity levels are discussed. Use of highly enriched (57)Fe as target material would lead to formation of high-purity (57)Co