First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Measurement of Compton Scattering at MAMI for the Extraction of the Electric and Magnetic Polarizabilities of the Proton.

A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, ß_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.

Single π 0 production off neutrons bound in deuteron with linearly polarized photons.

The quasifree γ → d → π 0 n ( p ) photon beam asymmetry, Σ , has been measured at photon energies, E γ , from 390 to 610 MeV, corresponding to center of mass energy from 1.271 to 1.424 GeV, for the first time. The data were collected in the A2 hall of the MAMI electron beam facility with the Crystal Ball and TAPS calorimeters covering pion center-of-mass angles from 49 ∘ to 148 ∘ . In this kinematic region, polarization observables are sensitive to contributions from the Δ ( 1232 ) and N(1440) resonances. The extracted values of Σ have been compared to predictions based on partial-wave analyses (PWAs) of the existing pion photoproduction database. Our comparison includes the SAID, MAID and Bonn-Gatchina analyses; while a revised SAID fit, including the new Σ measurements, has also been performed. In addition, isospin symmetry is examined as a way to predict π 0 n photoproduction observables, based on fits to published data in the channels π 0 p , π + n and π - p .

Helicity-Dependent Cross Sections for the Photoproduction of π

The double-polarization observable E and helicity-dependent cross sections σ_{1/2}, σ_{3/2} have been measured for the photoproduction of π^{0} pairs off quasifree protons and neutrons at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup. A circularly polarized photon beam was produced by bremsstrahlung from longitudinally polarized electrons and impinged on a longitudinally polarized deuterated butanol target. The reaction products were detected with an almost 4π covering calorimeter. The results reveal for the first time the helicity- and isospin-dependent structure of the γN→Nπ^{0}π^{0} reaction. They are compared to predictions from reaction models in view of nucleon resonance contributions and also to a refit of one model that predicted results for the proton and for the neutron target. The comparison of the prediction and the refit demonstrates the large impact of the new data.

Signatures of the d

We report a measurement of the spin polarization of the recoiling neutron in deuterium photodisintegration, utilizing a new large acceptance polarimeter within the Crystal Ball at MAMI. The measured photon energy range of 300-700 MeV provides the first measurement of recoil neutron polarization at photon energies where the quark substructure of the deuteron plays a role, thereby providing important new constraints on photodisintegration mechanisms. A very high neutron polarization in a narrow structure centered around E_{γ}∼570 MeV is observed, which is inconsistent with current theoretical predictions employing nucleon resonance degrees of freedom. A Legendre polynomial decomposition suggests this behavior could be related to the excitation of the d^{*}(2380) hexaquark.

Study of η and η' Photoproduction at MAMI.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

Insight into the Narrow Structure in η Photoproduction on the Neutron from Helicity-Dependent Cross Sections.

The double polarization observable E and the helicity dependent cross sections σ_{1/2} and σ_{3/2} were measured for η photoproduction from quasifree protons and neutrons. The circularly polarized tagged photon beam of the A2 experiment at the Mainz MAMI accelerator was used in combination with a longitudinally polarized deuterated butanol target. The almost 4π detector setup of the Crystal Ball and TAPS is ideally suited to detect the recoil nucleons and the decay photons from η→2γ and η→3π^{0}. The results show that the narrow structure previously observed in η photoproduction from the neutron is only apparent in σ_{1/2} and hence, most likely related to a spin-1/2 amplitude. Nucleon resonances that contribute to this partial wave in η production are only N 1/2^{-} (S_{11}) and N 1/2^{+} (P_{11}). Furthermore, the extracted Legendre coefficients of the angular distributions for σ_{1/2} are in good agreement with recent reaction model predictions assuming a narrow resonance in the P_{11} wave as the origin of this structure.

Cell proliferation and drug sensitivity of human glioblastoma cells are altered by the stable modulation of cytosolic 5'-nucleotidase II.

Cytosolic 5'-nucleotidase II (cN-II) has been reported to be involved in cell survival, nucleotide metabolism and in the cellular response to anticancer drugs. With the aim to further evaluate the role of this enzyme in cell biology, we stably modulated its expression the human glioblastoma cell ADF in which the transient inhibition of cN-II has been shown to induce cell death. Stable cell lines were obtained both with inhibition, obtained with plasmids coding cN-II-targeting short hairpin RNA, and stimulation, obtained with plasmids coding Green Fluorescence Protein (GFP)-fused wild type cN-II or a GFP-fused hyperactive mutant (GFP-cN-II-R367Q), of cN-II expression. Silenced cells displayed a decreased proliferation rate while the over expressing cell lines displayed an increased proliferation rate as evidenced by impedance measurement using the xCELLigence device. The expression of nucleotide metabolism relevant genes was only slightly different between cell lines, suggesting a compensatory mechanism in transfected cells. Cells with decreased cN-II expression were resistant to the nucleoside analog fludarabine confirming the involvement of cN-II in the metabolism of this drug. Finally, we observed sensitivity to cisplatin in cN-II silenced cells and resistance to this same drug in cN-II over-expressing cells indicating an involvement of cN-II in the mechanism of action of platinum derivatives, and most probably in DNA repair. In summary, our findings confirm some previous data on the role of cN-II in the sensitivity of cancer cells to cancer drugs, and suggest its involvement in other cellular phenomenon such as cell proliferation.

The purine analog fludarabine acts as a cytosolic 5'-nucleotidase II inhibitor.

For several years the IMP/GMP-preferring cytosolic 5'-nucleotidase II (cN-II) has been considered as a therapeutic target in oncology. Indeed, various reports have indicated associations between cN-II expression level and resistance to anticancer agents in several cancer cell lines and in patients affected with neoplasia, mainly by hematologic malignancies. In this paper we present evidence showing that, among the commonly used cytotoxic nucleoside analogs, fludarabine can act as a cN-II inhibitor. In vitro studies using the wild type recombinant cN-II demonstrated that fludarabine inhibited enzymatic activity in a mixed manner (Ki 0.5 mM and Ki' 9 mM), whereas no inhibition was observed with clofarabine and cladribine. Additional experiments with mutant recombinant proteins and an in silico molecular docking indicated that this inhibition is due to an interaction with a regulatory site of cN-II known to interact with adenylic compounds. Moreover, synergy experiments between fludarabine and 6-mercaptopurine in human follicular lymphoma (RL) and human acute promyelocytic leukemia (HL-60) cells transfected with control or cN-II-targeting shRNA-encoding plasmids, showed synergy in control cells and antagonism in cells with decreased cN-II expression. This is in line with the hypothesis that fludarabine acts as a cN-II inhibitor and supports the idea of using cN-II inhibitors in association with other drugs to increase their therapeutic effect and decrease their resistance.

Nutritional assessment and surgical infections in patients with gastric cancer or peptic ulcer.

Recent reports provide evidence that cancer is frequently associated with malnutrition and infection. This is particularly evident when the gastrointestinal tract is involved. The purpose of this study is to investigate the difference between the nutritional status of patients with gastric cancer and with peptic ulcer, and to determine which of the nutritional indicators may be of value in identifying patients with high risk of postoperative infections. A complete nutritional assessment was performed at admission and the following parameters were determined: hemoglobin, total serum protein, albumin, ceruloplasmin, retinol binding protein, transferrin; Fe; urine creatinine, creatinine/height index, arm muscle circumference; ideal body weight, usual body weight, arm circumference, triceps skinfold; lymphocytes, white blood cells, C3c, skin tests to recall and primary antigens. In the cancer patient group, hemoglobin, total protein, albumin, Fe, percentage usual body weight, and delayed hypersensitivity response to skin antigens were significantly more impaired than in controls. Preoperative delayed hypersensitivity response was the only test in correlation with the tumor stage. It was also significantly different in the gastric cancer patients who developed postoperative infections.

[Controlled study of unspecific cellular immunity in cancer patients]. / Studio controllato dell'immunità cellulare aspecifica in pazienti neoplastici.

Cellular immunity has been studied in 92 patients with solid tumors undergoing surgery, in order to evaluate immunocompetence at the time of diagnosis and to assess the prognostic value of parameters of cellular immunity. The results show that total lymphocyte counts, T-lymphocyte counts and lymphocyte blastogenic responses are moderately depressed at diagnosis in the cancer patients as compared to age matched controls. These parameters of cell mediated immunity "in vitro" seem to be of limited prognostic value, since no correlation was found with the clinical course during the first 6 postoperative months. Depression of delayed hypersensitivity response to cutaneous antigens appeared to be an index of poor prognosis.

[Immunological monitoring of patients operated on for epidermoid bronchogenic carcinoma]. / Monitoraggio immunologico di pazienti operati per carcinoma broncogeno epidermoidale.

Sequential monitoring of non specific immunity has been carried out in 16 patients with squamous cell bronchogenic carcinoma undergoing radical surgery. At the time of diagnosis total lymphocyte counts, T-lymphocyte counts and the blastogenic response of lymphocytes to PHA were only slightly depressed; on the contrary C3c and C4 serum levels were significantly increased (P less than 0.01). Sequential determinations of the immunologic profile at monthly intervals up to the 12th postoperative month showed a transient increase of total lymphocyte and T-lymphocyte levels; the lymphocyte blastogenic response to PHA and also C3c and C4 serum levels progressively decreased. Delayed hypersensitivity response to cutaneous antigens, neutrophil chemotaxis, serum levels of IgG, IgA, IgM and B-lymphocyte counts were constantly found within normal range.

Nutritional and immunological evaluations in cancer patients. Relationship to surgical infections.

Several reports provide evidence of the synergism between malnutrition and infection in hospitalized patients. In this study, preoperative complete nutritional assessment (NA) was performed to: 1) evaluate NA modifications in 21 controls with benign minor surgical diseases and in 71 surgical cancer patients; 2) determine the relative value of nutritional and immunological indicators in relation to the postoperative septic complications in cancer patients. The following parameters were used: percent weight loss/month, percent standard arm circumference, percent standard triceps skinfold; hematocrit, hemoglobin, serum proteins, albumin, iron, transferrin, ceruloplasmin, retinol binding protein (RBP); serum creatinine, urine creatinine, creatinine/height index, percent arm muscle circumference; peripheral lymphocytes, white blood cells, complement (C3c), skin tests. In the cancer group percent usual body weight, percent arm muscle circumference, hematocrit, hemoglobin, albumin, iron, ceruloplasmin, retinol binding protein, C3c and delayed hypersensitivity response (DHR) were significantly different from controls. Ceruloplasmin and DHR were the only tests significantly different in the cancer patients who developed postoperative infections. Duration of anesthesia and operative field contamination are other important causative factors which, if associated with malnutrition, may determine a higher susceptibility to infections in surgical cancer patients.