Crab cavities for linear colliders

Crab cavities have been proposed for a wide number of accelerators and interest in crab cavities has recently increased after the successful operation of a pair of crab cavities in KEK-B. In particular crab cavities are required for both the ILC and CLIC linear colliders for bunch alignment. Consideration of bunch structure and size constraints favour a 3.9 GHz superconducting, multi-cell cavity as the solution for ILC, whilst bunch structure and beam-loading considerations suggest an X-band copper travelling wave structure for CLIC. These two cavity solutions are very different in design but share complex design issues. Phase stabilisation, beam loading, wakefields and mode damping are fundamental issues for these crab cavities. Requirements and potential design solutions will be discussed for both colliders.Comment: 3 pages. To be published in proceedings of LINAC 2008, Victoria, Canad

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus

The goal of this study is to clarify whether the expression of metallothionein (MT) could affect the prognosis and the metastatic potential of squamous cell carcinoma (SCC) of the oesophagus. In paraffin-embedded specimens resected from 57 patients, MT mRNA and protein expressions were detected by in situ hybridization and immunohistochemistry respectively. The expression of MT was evaluated in respect of clinicopathologic variables and patients' survival. MT mRNA expression was significantly associated with the proportion of lymph node metastasis (71% in MT mRNA-positive tumours vs 42% in MT mRNA-negative tumours; P = 0.0343) and that of distant metastasis (29% in MT mRNA-positive tumours vs 5% in MT mRNA-negative tumours; P = 0.0452). In respect of MT protein expression, the frequency of distant metastasis was more common in MT-positive tumours than in MT-negative tumours (30% in MT-positive tumours vs 8% in MT-negative tumours; P = 0.0446). The survival rate of the patients with MT protein-negative tumours was significantly better than that of the patients with MT protein-positive tumours (P = 0.0340). There was a positive correlation between the expression of MT protein and that of proliferating cell nuclear antigen (P = 0.0018). Therefore, we conclude that MT expression, both at the mRNA and protein levels, may be a potential marker predicting metastatic and proliferative activities of oesophageal SCC. © 1999 Cancer Research Campaig

Specificity and Mechanisms for Induction of PDE4 Up-Regulation by PGE2 and Related Agents in Lung Fibroblasts

Introduction Prostaglandin E2 (PGE2) is an important modulator of the fibrotic changes that occur in pulmonary fibrosis and COPD. It is important to understand the mechanisms that regulate the initiation and desensitization of lung fibroblast responses to PGE2. Our previous studies (Am J Respir Crit Care Med 191:A4945, 2015) showed that pretreating lung fibroblasts with PGE2 induced a desensitization of PGE2 stimulation of cyclic AMP (cAMP) accumulation that could be reversed by the phosphodiesterase 4 (PDE4) inhibitor roflumilast. PGE2 did not reduce the cAMP response to the beta-adrenergic receptor agonist isoproterenol (Iso), and Iso pretreatment reduced the response to Iso but not to PGE2. The current study more directly examined the specificity and mechanisms of PGE2 desensitization with direct assays of PDE enzyme activity. Methods Human fetal lung (HFL-1) fibroblasts were incubated with or without 100 nM PGE2, 10 uM Iso, or 30 uM forskolin (Fsk) for 24 hr. Cells were washed to remove pretreatment drug and then lysed for PDE4 enzyme activity assays with cell lysates. Results Pretreatment of cells with PGE2 induced a 2- to 3-fold increase in PDE enzyme activity in cell lysates, and this increased cAMP breakdown was largely reduced by including the PDE4 inhibitor roflumilast. With 24-hr pretreatments, half-maximal increases in PDE activity occurred between 1 and 10 nM PGE2. With 100 nM PGE2 pretreatments, half-maximal increases occurred between 3 and 6 hrs. In contrast to PGE2 pretreatment, pretreatment with Iso induced little or no increase in PDE activity. Although Iso did not mimic the PGE2-induced increase in PDE activity, pretreatment with the direct adenylyl cyclase activator Fsk did induce an increase in PDE activity. The mRNA synthesis inhibitor actinomycin D (2 ug/mL) and the protein synthesis inhibitor cycloheximide (5 uM) nearly completely eliminated the PGE2-induced increase in PDE activity. Conclusions Pretreatment of HFL-1 fibroblasts with PGE2, but not with Iso, induces an increase in PDE enzyme activity that is inhibited by roflumilast, implicating PDE4 as the up-regulated isozyme. The ability of receptor-independent elevation of cAMP with Fsk to up-regulate PDE activity implicates cAMP as the likely mediator of the PDE up-regulation; the failure of cAMP elevation by Iso to induce the same response is likely related to differential localization and signaling by PGE receptors vs. beta-2 adrenergic receptors (Am J Physiol - Cell Physiol 298:L819, 2010). The inhibition by actinomycin D and cycloheximide suggests that transcriptional and translational processes mediate an up-regulation of PDE enzyme expression. These adaptive changes in PDE activity due to cAMP elevation will be important considerations for future studies to explore either PGE- or PDE-targeted therapies for fibrotic diseases of the lung

Study of a monolithic silicon telescope for solid state microdosimetry: Response to a 100 MeV proton beam

A monolithic silicon telescope was recently proposed and studied for solid state microdosimetry. It consists of a thin surface ∆E stage (about 2 μm in thickness), at study for silicon microdosimetry, coupled to an E stage about 500 μm in thickness, which provide information about the energy of the impinging particle. In order to study the response of the detection system to high energy charged hadrons, the silicon telescope was placed in a polystyrene phantom and irradiated with a 100 MeV un-modulated proton beam at the Loma Linda University Medical Centre. The experimental results were compared with those obtained with a numerical study based on Monte Carlo simulations carried out with the FLUKA code. The agreement between experimental and simulation results was satisfactory

Histological alterations in ovaries of pubertal female rats induced by triphenyltin

Triphenyltin is an organotin compound that has been used extensively as an antifouling biocide and as an agricultural pesticide. Certain organotin compounds act as endocrine-active agents and have been reported to affect reproduction in mollusks and mammals. Here we studied the histopathological effects of 2 or 6 mg triphenyltin chloride (TPTCl)/kg b.w. on the reproductive tissue and the thymus of female pubertal rats as part of a comprehensive pubertal assay. Beginning at postnatal day (PND) 23 female Wistar rats were treated daily per gavage until their first estrus after PND 53. Reproductive organs were removed and histologically evaluated. While no histological changes were observed in oviduct, uterus, vagina and mamma, an increase in the number of all follicle stages occurred at both dose levels. Furthermore, exposure to 2 mg TPTCl/kg b.w. led to a significant reduction in the diameter of tertiary follicles. A significant increase in the number of atretic follicles was observed in tertiary and preovulatory follicles after exposure to 6 mg TPTCl. The thymus displayed a decreased number of apoptotic cells in both dose groups. We conclude that peripubertal administration of 2 and 6 mg TPTCl/kg b.w. caused effects on ovarian follicles of female rats