CLIC (compact linear collider) is a future e+e− collider based on normal-conducting technology, currently under study at CERN. Its design is based on a novel two-beam acceleration scheme. The main beam gets RF power extracted from a drive beam through power extraction and transfer structures (PETS). The technical feasibility of CLIC is currently being proved by its Third Test Facility (CTF3) which includes the CLIC experimental area (CLEX). Two Double Length CLIC PETS will be installed in CLEX to validate their performance with beam. This paper is focused on the engineering design, fabrication and validation of this PETS first prototype. The design consists of eight identical bars, separated by radial slots in which damping material is located to absorb transverse wakefields, and two compact couplers placed at both ends of the bars to extract the generated power. The PETS bars are housed inside a vacuum tank designed to make the PETS as compact as possible. Several joint techniques such as vacuum brazing, electron beam and arc welding were used to complete the assembly. Finally, several tests such as dimensional control and leak testing were carried out to validate design and fabrication methods. In addition, RF measurements at low power were made to study frequency tuning.

The procurement of 103 superconducting magnet packages is part of the Spanish in-kind contribution to the European X-FEL. Each package consists of a main superferric quadrupole and two steerers, vertical and horizontal, fed by conduction-cooled current leads and enclosed in a stainless steel vessel. The operation temperature is 2 K, as they are embedded in a superfluid helium bath. The magnetic and mechanical designs are published elsewhere. The magnets are being produced in the Spanish company ANTEC, while the vessels are fabricated by another Spanish company, Trinos Vacuum-Projects, which is also responsible for the integration, under the supervision of CIEMAT. The helium vessel manufacturer needs to accomplish the requirements given by the European Pressure Equipment Directive, namely PED 97/23/EC. This paper describes the series fabrication techniques, the production follow-up, the quality assurance, and the magnet testing at the manufacturer site. Cold tests are realized at DESY premises. The main problems found during the fabrication of the first half of the series are also reported: 1) the reproducibility of the quadrupole coil dimensions; 2) the accuracy of the beam position monitor housing after final welding of the vessel; and 3) the minimization of the magnetization effects on the transfer function of the magnets.

CIEMAT has been working on the RF power extractor so-called PETS (Power Extraction and Transfer Structure) for the CLIC Test Facility 3 (CTF3) since 2007. The first contribution has been installed at the Test Beam Line (TBL). Additionally, a new PETS configuration is presently under fabrication at CIEMAT and will be installed in the Test Module at CTF3. This paper describes the PETS prototypes design, fabrication and assembly techniques. The characterization of the devices with low RF power is also described.

The goal of the present CLIC Test Facility (CTF3) is to demonstrate the technical feasibility of the CLIC scheme, where the RF power extracted from the drive beam is used to accelerate the main beam. Several prototypes of the RF power extractor so-called PETS (Power Extraction and Transfer Structure) have been developed at CIEMAT for this facility. The first device was embedded in a steel vacuum tank and installed at the Test Beam Line (TBL), whose aim is to prove the beam stability during deceleration and power extraction. Presently, CERN and CIEMAT share the responsibility to build eight additional PETS for TBL. Finally, in the framework of EuCARD (European Coordination for Accelerator Research and Development) collaboration, a new PETS configuration is presently under engineering design at CIEMAT. It is based on a compact concept developed at CERN. This device will be installed in the Test Module at CTF3, in a similar configuration to that of the final two-beam scheme acceleration of CLIC. This paper describes the PETS prototype fabrication techniques used at CIEMAT, with particular attention to the production of the long copper rods which induce the RF generation and the welding and assembly procedures. The characterization of the devices with low RF power and the first tests with beam are also described.

This paper resumes the study of the development of high precision joints performed by vacuum brazing as part of the fabrication of accelerating structures and other parts of particle accelerators. The study is focused on the selection of the most suitable parameters for carrying out high quality copper/copper and copper/stainless steel joints such as thermal cycle, filler material, filler grooves design, surface preparation, thickness of Ni plating and joint clearance. The joint characterization was carried out by means of microstructural (OM, SEM) and compositional (EDS) techniques and by leaking test.

The superconducting combined magnets for the main linac are part of the Spanish contribution to XFEL. Each magnet consists of a super-ferric quadrupole for focusing and two dipoles (horizontal and vertical) for steering, glued on the beam tube. The magnets will be operated in a superfluid helium bath. The aperture is 78 mm. The quadrupole gradient is 35 T/m whereas each dipole field is about 0.04 T. This paper reports about the magnetic measurements made on the first prototype. Measured field quality matches calculated values, both at room and cold conditions. Magnetization has been also measured in all the coils, with single or combined powering. Asymmetric and strongly non-linear transfer functions have been observed when quadrupole and dipoles were powered simultaneously. On the other hand, detailed computations were made with ROXIE to understand that issue. Results matched measurements when only one set of coils was powered, but not when two of them were energized. It is likely that the effect of the transport current or the coil-ends-which are not modeled by ROXIE-could explain the difference.

Background: Radiofrequency catheter ablation is a well‐established approach to treating several types of cardiac arrhythmias. The aim of our study was to provide data on the diffusion of catheter ablation procedures in clinical practice through a meta‐analysis of National Registries of electrophysiological procedures performed over a 5‐year period, from 2000 to 2005. Methods: We found only two national registries of catheter ablation procedures published in the journals indexed in PubMed: The Spanish Catheter Ablation Registry and the Portuguese National Registry on Cardiac Electrophysiology. In addition, we included in our analysis the data from the Italian Registry of Electrophysiological Procedures. Results and Conclusions: This meta‐analysis revealed a steady increase in the total number of catheter ablation procedures, particularly for the ablation of atrial flutter, of tachycardia due to double nodal pathways, and of the left atrial substrate in atrial fibrillation. However, the progress of catheter ablation and the impetus for additional research and development of new approaches and technologic advances requires further data on clinical indications, methodologic approach, complications, and long‐term success rate in the real world.

This paper introduces an effective technique for reducing semiconductor switching losses, and evenly distributing them, in current-controlled single-phase inverters. The current switching frequency is reduced taking advantage of three-level commutation by a double hysteresis-band current-control strategy imported from multilevel converters studies. Furthermore, an additional reduction of the semiconductor switching frequency is accomplished by modifying the standard semiconductor switching pattern for balancing power dissipation between upper and lower devices. An overall reduction of switching losses in a factor of 2 to 4 is achieved in this manner. The system control strategies are exposed in detail and experimental results for a 200 kVA grid-side converter of a switched reluctance drive are presented to better show the concepts involved.

In the CLIC concept, PETS (Power Extraction and Transfer Structure) role is to decelerate the drive beam and transfer RF power to the main beam. One of the CTF3 test beam line (TBL) aims is to study the decelerated beam stability and evaluate PETS performance. The PETS core is made of eight 800 mm long copper rods, with very tight tolerances for shape (+/20 micron), roughness (less than 0.4 micron) and alignment (+/0.1 mm). Indeed, they are the most challenging components of the tank. This paper reports about the methods of fabrication and control quality of these bars. A special test bench has been designed and manufactured to check the rod geometry by measuring the RF fields with an electric probe. Other parts of the PETS tank are the power extractor, the waveguides and the vacuum tank itself. Industry is partially involved in the prototype development, as the series production consists of 15 additional units, and some concepts could be even applicable to series production of CLIC modules.

The design of a HTS cryogen-free solenoid for a gyrotron magnet upgrade is presented. This gyrotron is used to set up and warm the plasma in an experimental fusion device at Ciemat. The solenoid will be wound with BISCCO-2223 tapes. A two stage Gifford-McMahon cryocooler will be used to cool down the magnet. A significant operation cost will be saved as the present solenoid is a Nb-Ti magnet cooled down in a helium bath supplied with mobile tanks. The main requirement of the magnet is to reproduce the original magnetic profile in the axis of the solenoid with a peak of 2 T in a 150 mm diameter warm bore. The magnet consists of several stacked double-pancake coils. The outer radii, the axial positions and the number of windings have been optimized by means of a genetic algorithm. Afterwards, the cryostat design is also described, including the heat leakage calculation. Finally, the winding techniques and the results of the tests of a prototype coil are also reported in this paper.

OBJECTIVE:To report the oral rehabilitation of velopharyngeal insufficiency due to a congenital anatomic defect using an implant-retained speech-aid prosthesis.CASE REPORT:A 65-year-old man with a diagnosis of complete unilateral cleft lip and palate on the left side with an unrepaired palate was examined. A removable partial denture with a speech bulb had been used for approximately 40 years. After primary care for gross caries and tooth mobility, an implant-retained obturator with a speech bulb was fabricated.RESULTS AND CONCLUSION:Improvement in mastication, speech, and velopharyngeal function was achieved with a satisfactory esthetic result.

An international collaboration at DESY is currently studying the possibilities of a new type of particle accelerator: the superconducting linear collider, developed under the project name TESLA. The TESLA Test Facility is trying to establish a well-developed collider design, which will also be helpful for the design of a superconducting X-ray Free Electron Laser facility (XFEL), a project approved by the German Government and now in its initial stage. Besides, XFEL will be the ideal workbench to improve the necessary components for the next International Linear Collider (ILC). This paper is about the fabrication and testing of the first prototype of a combined superconducting magnet for focusing and steering purposes, in the framework of the Spanish contribution to the TESLA project. It consists of a quadrupole and two dipole concentric coils, one horizontal and another one, vertical. The double pancake winding technique with a ribbon of eight pre-glued wires has been used in order to develop a cheap method for the quadrupole coils in industrial scale, as the accelerator would need about 800 magnets. The coils were fully instrumented with voltage taps to study the quench propagation. The magnet has been successfully tested at DESY and the results are reported in this paper

NOD mice spontaneously develop insulitis and type 1 diabetes (T1D) mellitus similar to humans. Insulitis without overt disease occurs in the BDC2.5 TCR-transgenic NOD mice that express the rearranged TCR alpha- and beta-chain genes of a diabetogenic T cell clone reactive to an unknown beta cell autoantigen. A previous study identified an extensive panel of peptides that are highly active in stimulating T cells from transgenic BDC2.5 mice in culture. However, none of these peptides cause active disease in NOD and BDC2.5 animals or in NOD recipients of adoptively transferred BDC2.5 T cells following direct immunization in vivo. We show that direct immunization of transgenic BDC2.5 mice causes many BDC2.5 T cells to become activated and apoptotic. Strikingly, soluble peptides administered to recipients of activated, highly pathogenic BDC2.5 T cells results in protection from disease. These results suggest that high affinity peptide analogues of autoimmune epitopes might be useful as therapeutic modulators in active autoimmune disease.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently used in preclinical and clinical protocols to modulate autoimmune responses, bone marrow transplants, and recovery from immune ablative therapies. The immunological outcome of such therapies is not fully understood. We tested the hypothesis that GM-CSF would enhance the maturation of antigen-presenting cells, facilitating presentation of beta-cell autoantigens to autoreactive T cells. We found that islet expression of GM-CSF greatly enhanced disease in male mice. Islet-derived APC but not splenic APC showed markedly enhanced capacity to stimulate in vitro proliferative responses of islet-antigen-specific autoreactive T cells. In vivo transfer of CD8(+) and CD4(+) T cells demonstrate that autoreactive T cells undergo extensive division in pancreatic lymph nodes of GM-CSF-transgenic mice compared with wild-type NOD male mice. Together, the results presented here demonstrate that expression of GM-CSF in the pancreas can enhance autoimmunity in disease-susceptible mice.

The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable. In SJL mice, reinfection with CB4 enhanced the development of hyperglycemia. As predicted, the immune system responded more rapidly to the second infection and virus was cleared more swiftly. However, while infiltrating T cells were found within the pancreas, depletion of the CD4 T cell population prior to secondary infection or use of CD8 knock-out mice had no effect on the development of virus-mediated hyperglycemia. In conclusion, enhanced hyperglycemia induced by CB4 occurs independent of the T cell response.

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged beta cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice harboring a diabetogenic T cell repertoire with either the islet-damaging agent streptozotocin (STZ) or poly I:C, which nonspecifically activates T cells. Significantly, only treatment of mice with STZ resulted in IDDM and mimicked the effects observed following CB4 infection. Furthermore, antigen-presenting cells from STZ-treated mice were shown to directly activate autoreactive T cells and induce diabetes. Therefore, the primary role of CB4 in the precipitation of IDDM is to damage tissue, causing release and presentation of sequestered islet antigen. These events stimulate autoreactive T cells and thereby initiate disease.

Coxsackieviral infections have been linked etiologically to multiple diseases. The serotype CB4 is associated with acute pancreatitis and autoimmune type 1 diabetes. To delineate the mechanisms of host survival after an acute infection with CB4 (strain E2), we have investigated the role of nitric oxide (NO), generated by the inducible form of nitric oxide synthase (NOS2), in viral clearance and pancreatic beta-cell maintenance. Mice deficient in NOS2 (NOS2-/- mice) and their wild-type (wt) counterparts were injected with CB4, after which both groups developed severe pancreatitis, hepatitis, and hypoglycemia within 3 days. Within 4 to 7 days postinfection (p.i.), most of the NOS2-/- mice died and at a strikingly higher mortality rate than wt mice. Histological examination of pancreata from both infected NOS2-/- and infected wt mice revealed early and complete destruction of the pancreatic acinar tissue, but intact, insulin-stained islets. When examined up to 8 weeks p.i., neither surviving NOS2-/-mice nor surviving wt mice developed hyperglycemia. However, the clearance of infectious CB4 was different between the mice. The spleens of NOS2-/- survivors were cleared of infectious virus with kinetics similar to that of wt mice, but the livers, pancreata, kidneys, and hearts of the NOS2-/- groups cleared virus more slowly than those of the wt group. This delayed clearance was particularly prominent in the livers of infected NOS2-/- mice, which also showed prolonged histopathological features of viral hepatitis. Taken together, this outcome suggests that NOS2 (and NO) is not required for the prevention of pancreatic beta-cell depletion after CB4 infection. Instead the critical actions of NOS2 apparently occur early in the host immune response, allowing mice to survive and clear virus. Moreover, the data support the existence of an organ-specific dependency on NO for a rapid clearance of CB4.

Several findings have recently questioned the long held hypothesis that cytokines belonging to the Th2 pathway are protective in T-cell-mediated autoimmunity. Among them, there is our previous report that pancreatic expression of IL-4 activated islet antigen-specific BDC2.5 T cells and rendered them able to trigger insulin-dependent diabetes mellitus in ins-IL-4/BDC2.5 mice (Mueller et al., Immunity, 7, 1997). Here we analyze the mechanisms underlying IL-4-mediated activation of the self-reactive BDC2.5 T cells. IL-4 is mainly known as the Th2-driving cytokine. However, IL-4 is also critical for DC maturation and upregulation of antigen uptake and presentation by macrophages. In our model, we found that pancreatic expression of IL-4 activated self-reactive BDC2.5 T cells by increasing islet antigen presentation by macrophages and dendritic cells. IL-4 could have triggered self-antigen presentation within the pancreatic islets both by driving maturation of DC from a tolerizing to a priming state and by increasing self-antigen uptake by macrophages.