Analysis of longitudinal bunching inan FEL driven two-beam accelerator

Recent experiments [1] have explored the use of a free-electron laser (FEL) as a buncher for a microwave two-beam accelerator, and the subsequent driving of a standing-wave rf output cavity. Here we present a deeper analysis of the longitudinal dynamics of the electron bunches as they are transported from the end of the FEL and through the output cavity. In particular, we examine the effect of the transport region and cavity aperture to filter the bunched portion of the beam. [1] T. Lefevre, et. al., Phys. Rev. Lett. 84 (2000), 1188.Comment: 3 pages, 8 figures. Submitted to XX Int'l LINAC Conferenc

Performance Pay for Teachers: A Comparative Multi-Case Study

Voluminous studies of performance-based compensation for teachers have been conducted to ascertain the dynamics of programs that are successful in improving teacher effectiveness and in turn student achievement. Few studies have concentrated on what the perceptions of teachers are on performance-based compensation models and what they consider fair and equitable components and structures of such models. This study surveyed four school districts that had the Teacher Advancement Program (TAP) model and four school districts that did not have a performance pay model associated with their school districts. The research questions that guided the study were: “How do teachers in TAP school districts perceive the performance pay components of TAP?” and “How do teachers in non-performance pay schools perceive performance pay program components?” and finally, “How do these two groups of teachers’ perceptions compare to one another about performance pay models?” Comparing the findings from the data analysis, both the TAP and non-TAP districts agreed that performance pay components might cause resentment among staff members, undermine staff morale, and create an atmosphere where teachers would be less willing to assist colleagues. Focus group interviews were conducted at three campuses from a TAP school district to gain in-depth insight on how teachers really perceived the components of the specific program implementation in their school district. Four themes emerged from the data analysis of the focus group interviews: (a) transparency and communication of procedures, (b) reliability of observations and evaluations of teachers, (c) additional workload for teachers not worth the extra pay, and (d) increased professional development worthwhile. While studies show that implementation of the TAP program with fidelity has increased student achievement based on test scores, the results of this study suggested that performance pay components within the surveyed schools was not a favorable way of increasing teacher pay. Future research should include compensation models that can be constructed without using test scores as a major component and increasing the amount of teacher input to construct the program

Radiation induces p38-mediated endothelial cell death through ceramide generation and membrane remodeling

Involvement of sphingolipid ceramide and its metabolic enzyme, the acid sphingomyelinase (ASM) in irradiated microvascular endothelial cells have been demonstrated in lungs, small intestines and tumors murine models. However, molecular mechanisms involved in the apoptotic pathway are poorly understood. Using the microvascular endothelial cell HMEC1, we showed that ceramide generation in the membrane appears within the five minutes following 15 Gy. Our recent work (Bonnaud, Cancer Research, 2007) showed that radiation-induced apoptosis detected within 24 hours is inhibited by treatment with pharmacological ASM inhibitors in HMEC1 cells and therefore prove the use of those cell line as a good in vitro model to study the ceramide mediated apoptosis after exposure to ionising radiation. High-dose irradiation is known to induce the death-pathway p38 in microvascular endothelial cells, other than HMEC-1. We also observed, in our cell model exposed to 15 Gy, a rapid p38 phosphorylation visualised by phosphoblot and immunofluorescence. p38 blockade by MAPK inhibitor III or shRNA decreased radiation induced death in HMEC-1. Link between ceramide generation and p38 activation has been made after studies of raft microdomain organisation into the cell membrane. In fact, ceramide is well-described to induce the coalescence of raft microdomains in several cell models after a large sprectrum of stresses, such as H2O2, cytokines, heat shock. We detected a raft-marker ganglioside GM1 relocalisation from a discrete pattern in the cell surface, to large and polarised areas, following irradiation. The two concomitant phenomena, i.e. ceramide-induced raft coalescence and p38 death-pathway activation, has been connected by use of drugs, such as nystatin, disorganizing raft formation, which inhibited radiation-induced raft coalescence, activation of p38 and the subsequent death-induction of microvascular cells. Molecular apoptotic pathway induced by radiation has been confirmed by addition of exogenous natural ceramide or bacterial bSM in HMEC-1, which induced membrane reorganisation, p38 activation and death. In the present work, a singular cell culture model allows to better describe the cascade of disconnected events leading to microvascular cell destruction in response to high dose of ionizing radiation

Acid Sphingomyelinase Secretion by Irradiated Endothelial Cells: A Role in Intestinal Epithelial Cell Damage?

Endothelial cell (EC) response has been implicated in the induction of intestinal damage following high dose radiation exposure. Furthermore, acid sphingomyelinase (ASM), a lipid hydrolase, has been shown to contribute to the pathophysiology of lung, liver, and heart dysfunction through increased amount of extracellular ASM. However, the potential role of ASM release in radiation-induced intestinal damage has not yet been considered. Therefore, the aim of this study was to investigate whether ASM production by EC is modulated by irradiation and implicated in epithelial cell damage. First, we set up a non contact coculture model with 15 Gy-irradiated EC (HMVEC-L) and non-irradiated T84 epithelial cells to examine whether in vitro irradiation of EC resulted in the induction of epithelial cell damage via paracrine pathway. Twenty-four hours following irradiation of EC, a decreased cell number (29%) and percentage in mitosis (66%) as well as increased apoptosis (1.5-fold) and cell-surface area (1.5-fold) were shown in non-irradiated T84 cells. Next, we assessed whether ASM might be a potential mediator of this observed bystander effect. Twenty-four hours following EC radiation exposure, ASM was measured both in endothelial cell culture supernatant and lysate by ASM activity assay and Western blot. We showed for the first time that irradiation of EC induced a significant 1.4-fold increased ASM activity in culture supernatant. A 1.4-fold increased ASM was also observed in EC lysate. Then, we determined the effect of exogenous ASM on T84 cells. Human placental ASM induced a dose-dependent decreased epithelial cell number and increased apoptosis. A concentration of 100 mU/ml of exogenous ASM recapitulated the deleterious effects in T84 cells observed in bystander coculture conditions and correlated with the calculated ASM concentration in irradiated EC culture supernatant. RNA interference of ASM is currently used to determine if silencing ASM in irradiated EC reduced epithelial cell damage. Finally, we measured ASM activity in serum of 15-Gy total body irradiated mice. We showed for the first time a 1.6-fold increase in serum ASM activity from 30 min to 4 h following radiation exposure. Together our data suggest that endothelial ASM may be a key mediator in the pathogenesis of radiation-induced intestinal dysfunction

The cytotoxic effect of combined hyperthermia and taxane chemotherapy on ovarian cancer cells: results of an in vitro study.

International audiencePURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is under continuous evaluation as a potential treatment for ovarian cancer. The purpose of this study was to evaluate the effect of chemotherapy, drug concentration and temperature. MATERIALS AND METHODS: We examined the combined effects of hyperthermia and taxane chemotherapy on the clonogenic survival of the human ovarian carcinoma SHIN-3 cell line in vitro. RESULTS: When hyperthermia was combined with chemotherapy, the median lethal dose (LD50) was equivalent regardless of the duration of exposure, and was independent of the exposure temperature. Taxanes showed a similar LD50 over the temperature range tested. CONCLUSIONS: In our study, hyperthermia does not increase the cytotoxic effects of taxanes, at least for the concentrations and durations tested

Analysis of longitudinal bunching in an FEL driven two-beam accelerator

Recent experiments have explored the use of a free-electron laser (FEL) as a buncher for a microwave two-beam accelerator, and the subsequent driving of a standing-wave rf output cavity. Here we present a deeper analysis of the longitudinal dynamics of the electron bunches as they are transported from the end of the FEL and through the output cavity. In particular, we examine the effect of the transport region and cavity aperture to filter the bunched portion of the beam

Mechanisms of Cell Sensitization to Alpha-Radioimmunotherapy by Doxorubicin or Paclitaxel in MultipleMyeloma Cell Lines

Purpose:The purpose of this studywas to analyze differentmechanisms (cell cycle synchronization, DNA damage, and apoptosis) that might underlie potential synergy between chemotherapy (paclitaxel or doxorubicin) and radioimmunotherapy with a radionuclides. Experimental Design:Threemultiplemyeloma cell lines (LP1, RMI 8226, and U266)were treatedwith 213Bi-radiolabeledB-B4, amonoclonal antibody that recognizes syndecan-1 (CD138) 24 hours after paclitaxel (1nmol/L) or doxorubicin (10 nmol/L) treatment.Cell survivalwas assessed using a clonogenic survival assay. Cell cycle modifications were assessed by propidium iodide staining and DNA strand breaks by the comet assay. Level of apoptosis was determined by Apo 2.7 staining. Results: Radiation enhancement ratio showed that paclitaxel and doxorubicin were synergistic with a radioimmunotherapy.After a 24-hour incubation, paclitaxel and doxorubicinarrested all cell lines in the G2-M phase of the cell cycle. Doxorubicin combined with a radioimmunotherapy increased tail DNA in the RPMI 8226 cell line but not the LP1or U266 cell lines compared with doxorubicin alone or a radioimmunotherapy alone. Neither doxorubicin nor paclitaxel combined with a radioimmunotherapy increased the level of apoptosis induced by either drug alone or a radioimmunotherapy alone. Conclusion: Both cell cycle arrest in the G2-M phase and an increase in DNA double-strand breaks could lead to radiosensitization of cells by doxorubicin or paclitaxel, but apoptosis would not be involved in radiosensitizationmechanisms.JRC.E.5-Nuclear chemistr

Therapeutic efficacy of alpha-riT Using a 213Bi-anti-hcD138 antibody in a Mouse Model of Ovarian Peritoneal carcinomatosis

Purpose: Ovarian peritoneal carcinomatosis is a pathology for which effective cures are currently lacking. New research protocols seek to eradicate residual micrometastases following cytoreductive surgery by using hyperthermic intraperitoneal chemotherapy (HIPEC) or radioimmunotherapy (RIT). This study aims to first develop alpha-RIT using an anti-CD138 mAb radiolabeled with an alpha-emitter, bismuth-213 (213Bi-B-B4) and HIPEC in a nude mouse model and second to compare and combine these techniques. Material and methods: A murine model of postoperative ovarian peritoneal carcinomatosis was established. A pilot group of six mice received an intraperitoneal injection of luciferase-tagged SHIN-3 cells and bioluminescence was measured every day. Cytoreductive surgery was performed at day 14 (n = 4) and 29 (n = 2). Because the residual bioluminescence signal measured after surgery was equivalent to that obtained 3 days after the graft, HIPEC or alpha-RIT treatments were applied 3 days after the graft. Ten mice were treated by HIPEC with cisplatine (37.5 mg/mL), 11 with 7.4 MBq of 213Bi-B-B4, seven with 11.1 MBq of 213Bi-B-B4, and 10 mice were treated with the combined therapy (HIPEC + 7.4 MBq of 213Bi-B-B4). Eleven mice received no treatment. Bioluminescence imaging and survival were assessed. Results: Alpha-RIT 7.4 MBq and 11.1 MBq significantly improved survival (p = 0.0303 and p = 0.0070, respectively), whereas HIPEC and HIPEC + alpha-RIT treatments did not significantly ameliorate survival as compared to the control group. Conclusion: Survival was significantly increased by alpha-RIT treatment in mice with peritoneal carcinomatosis of ovarian origin; however, HIPEC alone or in combination with alpha-RIT had no significant effect.JRC.E.5-Nuclear chemistr