In recent years we increased the typical maximum peak field on axis gradients obtained in L-band superconducting RF (SRF) photoinjector cavities at vertical tests to around 55 MV/m. This was achieved with niobium cathode plugs directly screwed to the cavity back wall omitting an RF choke filter and a load lock system for cathodes. Copper demonstrated being a suitable cathode material in normal conducting injector cavities used at X-Ray Free Electron Lasers (XFELs) operating with pulsed RF. In this article we present the first experimental confirmation that peak field on axis gradients around 55 MV/m and beyond can be achieved in L-band SRF photoinjector cavities with copper cathode plugs screwed to the cavity back wall. We view this as a major milestone for the development of a high gradient photoinjector operating continuous wave (CW).

At DESY, the development of a 1.6-cell, 1.3 GHz all superconducting gun cavity with a lead cathode attached to its back wall is ongoing. The special features of the structure like the back wall of the half-cell and cathode hole require adaptations of the procedures used for the treatment of nine-cell TESLA cavities. Unsatisfactory test results of two prototype cavities motivated us to re-consider the backwall design and production steps. In this contribution we present the status of the modified cavity design including accessories causing accelerating field asymmetries, like a pick up antenna located at the back wall and fundamental powerand HOM couplers. Additionally, we discuss preliminary considerations for the compensation of kicks caused by these components.

We report recent progress in the development of a hybrid lead/niobium superconducting RF (SRF) photoinjector. The goal of this effort is to produce an injector with the SRF properties of a niobium cavity along with the superior quantum efficiency (QE) of a lead photocathode. A prototype hybrid injector, consisting of an all-niobium cavity arc-deposited with lead in the cathode region, has been constructed. We present the results of QE measurements on this cavity under RF field, and an arc-deposited cathode under DC bias at cryogenic temperatures.

We report on the progress and status of an electron RF* gun made of two superconductors: niobium and lead [1]. The presented design combines the advantages of the RF performance of bulk niobium superconducting cavities and the reasonably high quantum efficiency of lead. The design of RF-gun and performance of 3 test cavities without and with the emitting lead spot are reported in this contribution. Measured quantum efficiency for lead at 2 K is presented briefly. More details are reported in [9].

We report recent progress in the development of a hybrid lead/niobium superconducting RF (SRF) photoinjector. The goal of this effort is to produce an injector with the SRF properties of a niobium cavity along with the superior quantum efficiency (QE) of a lead photocathode. Quantum efficiency measurements have been performed on an RF cavity with an electroplated lead plug as the photocathode. The effect of the laser on the RF performance of the cavity was characterized. Further measurements of the cavity RF performance are reported in these proceedings [6].

Die Augenoptik beschäftigt sich mit der Erstellung passender Sehhilfen für Fehlsichtige. Um dieser Aufga- be optimal gerecht zu werden, baut sie auf vielseitigen Grundlagen auf. Unter ihnen nimmt das Verstehen des Sehvorganges einen wichtigen Platz ein. Der Seh- vorgang kann untersucht werden auf Informationsauf- nahme, deren neuronale Verarbeitung und Interpre- tation. Dabei kommt den Blickbewegungen eine große Bedeutung zu, wird doch mit ihnen das Auge präzise in Richtung aller interessanten Blickziele ausgerichtet. Die genaue Kenntnis der Blickbewegungen hilft, die In- formationsaufnahme beim Sehen besser zu verstehen. Zur Erfassung dieser Blickbewegungen dienen speziel- le Messgeräte, sog. Eye-Tracker. Diesen Systemen fehlt aber oftmals eine anschauliche Darstellung der Blick- richtung, z.B. durch Einblendung eines Punktes in ein Live-Kamerabild bei gleichzeitiger hoher räumlicher und zeitlicher Auflösung. Auch sind die meisten am Markt verfügbaren Systeme nicht portabel einsetzbar, so dass nicht in alltäglichen Sehsituationen gemessen werden kann und der Proband an einen ortsfesten Auf- bau gefesselt ist. Dieser und der in der nächsten Ausgabe folgende Bei- trag beschreiben, wie ein handelsübliches Gerät im Rahmen einer Diplomarbeit

Local infusion of recombinant monocyte chemoattractant protein-1 (MCP-1) has been shown to enhance collateral artery formation in rabbit and pig hindlimb models. Owing to clinical disadvantages of protein infusion, a nonviral, liposome-based MCP-1 gene transfer was developed. Collateralization in a porcine hindlimb model served to provide a proof-of-principle for the functional benefit of MCP-1 overexpression. Development of arterial conductance as a measure of functionally relevant collateralization was evaluated in occluded as well as untreated hindlimbs in each animal. At the time of occlusion, MCP-1 and control DNA/DC-30 lipoplexes were transferred to femoral arteries of Goettingen minipigs (two therapeutic MCP-1 groups: 2 and 4 μg and one control group), using the Infiltrator ® local drug-delivery device. At 2 weeks following occlusion, collateralization was determined as changes in peripheral haemodynamic conductance, peripheral over aortic blood pressure ratio and angiographically visible morphology of the peripheral vessel tree. Nonviral MCP-1 gene transfer significantly improved peripheral conductance (control 11.69±2.78%, 2 μg 23.81±2.81%, P<0.05 and 4 μg 23.36±3.1%, P<0.05; n=12 per group) as well as the ratio of peripheral over aortic blood pressure (control 0.64±0.03%, 2 μg 0.75±0.02%, P<0.05 and 4 μg 0.75±0.02%, P<0.05; n=12 per group) when compared to the untreated controls 2 weeks after occlusion. Thus, it could be demonstrated for the first time that in situ overexpression of MCP-1 following local nonviral gene transfer is a potential approach to improve peripheral collateralization.

BACKGROUND:The recent success in the derivation of differentiated cell types from stem cells has raised prospects for the application of regenerative cell therapy. In particular, embryonic stem cells are attractive sources for cell transplantation, due to their immortality and rapid growth. These cells, however, also possess tumorigenic properties, which raises serious safety concerns and makes biosafety testing mandatory. Our goal was to establish a highly sensitive animal model for testing the proliferative potential of stem-cell grafts.METHODS:BALB/c nude mice received cell grafts of non-neoplastic MRC-5 cells containing defined numbers of mouse embryonic stem cells. We either injected 1 million viable cells into the kidney capsule, or mixed 2 million cells with Matrigel for s.c. transplantation. To analyze the possible impact of an intact immune response on tumor development, we also transplanted the cells into immunocompetent mice. Animals were sacrificed when the tumors became >1 cm and were analyzed in detail.RESULTS:The nude mouse model reproducibly allowed detection of 20 tumorigenic cells, and even as few as 2 ES cells were found to form teratoma. Interestingly, the administration of cell grafts at two different application sites resulted in different growth kinetics and tumor phenotypes. The highest level of sensitivity (100% detection of 20 tumorigenic ES cells) was achieved by s.c. injection of cells mixed with Matrigel. The influence of the immune system on tumor-cell development was demonstrated by a higher tumor rate of transplants in immunodeficient nude mice compared with immunocompetent mice.DISCUSSION:We have established a reliable animal model for routine assessment of the biosafety profile of stem-cell-derived cell transplants. This model will facilitate the generation of homogenous non-tumorigenic cell populations, and will help to integrate standardized safety systems into the application of stem-cell-derived grafts for clinical purposes.

BACKGROUND:Little is known about the natural course of internal carotid artery (ICA) occlusion and its possible recanalization. The present study was designed to evaluate recanalization rates of extracranial ICA occlusions in acute stroke patients by means of color-coded duplex sonography (CCDS).METHODS:305 patients with acute ischemia in the territory of the middle cerebral artery were included in this study. All patients had a neurological examination on admission and on discharge and were rated by means of the European Stroke Scale (ESS). Extracranial color-coded duplexsonography, transcranial Doppler sonography and cranial computed tomography were immediately performed after admission and within 7 days.RESULTS:254 patients showed no sign of hemodynamic relevant stenosis greater than 70% of the ICA. 21 patients had symptomatic high grade ICA stenosis. 20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to 77 years) with an acute atherothrombotic or cardioembolic occlusion showed a recanalization of the ICA in the follow-up ultrasonography. Two patients with cardiogenic embolic occlusion of the ICA had the most favorable outcome and these patients showed no residual stenosis. 4 patients who had ultrasound findings consistent with atherosclerosis on follow-up examination (2 high-grade stenosis, 2 with carotid plaques) did not show a notable improvement of their ESS-score. Patients with carotid plaques developed complete MCA infarctions; the other 4 patients had partial anterior circulation infarction on follow-up CT.CONCLUSIONS:The present study showed that recanalization of the occluded ICA in acute stroke patients is more frequent than generally presumed. CCDS should be routinely performed in the follow-up of stroke patients as spontaneous recanalization may influence clinical outcome.

According to clinical observations, cardiogenic embolism occurs more often in the anterior than in the posterior cerebral circulation. An ultrasound (US) contrast agent was used to artificially produce microembolic signals (MES) to imitate the intracranial distribution of systemic emboli. Systemic microemboli were simulated by IV administered US agent (Levovist(R) 300 mg/mL as bolus). A total of 20 patients were monitored by means of transcranial Doppler sonography (TCD), 3 min after the injection, with a 2-MHz transducer simultaneously at 50 mm (middle cerebral artery, MCA, on one side) and 90 mm (basilar artery, BA). Four 3-min recordings were done (two of the right MCA, two of the left MCA, with the BA, respectively). Three observers and an automatic detection system independently performed an off-line analysis. A total of 160 recordings were analyzed. The mean numbers of detected high-intensity transient signals (HITS) were 34.5 +/- 28.2 in the right MCA (simultaneously registered HITS in the BA: 9.4 +/- 16.8) and 39.1 +/- 34.2 in the left MCA (simultaneously registered HITS in the BA: 12.2 +/- 14.5). Only 21.4 to 23.7% of all HITS were recorded in the BA. Microembolic signals artificially produced by means of US contrast agent made it possible to mimic the physiologic distribution of small embolic particles. In future, these might help to investigate the distribution of systemic emboli in different vascular territories in various pathologic conditions of the cerebral blood flow.

BACKGROUND AND PURPOSE:Gray-scale harmonic imaging is the first method to visualize blood perfusion and capillary blood flow with ultrasound after intravenous contrast agent application. The purpose of the present study was to evaluate the potential of transient response second harmonic imaging (TRsHI) to assess normal echo contrast characteristics in different brain areas by transcranial ultrasound.METHODS:In 18 patients without cerebrovascular diseases, TRsHI examinations were performed bilaterally with the use of the transtemporal approach after application of 6.5 mL of a galactose-based microbubble suspension (400 mg/mL). The transmission rate was once every 4 cardiac cycles. Regional cerebral contrast was visually assessed and then quantified off-line with the use of time-intensity curves. In 4 different regions of interest (ROI) (posterior part of the thalamus [ROIa], anterior part of the thalamus [ROIb], lentiform nucleus [ROIc], and white matter [ROId]), the following parameters were evaluated: peak intensity, area under the curve (AUC), and time to peak intensity. AUC ratios for ROIc/a, d/a, c/b, and d/b were calculated.RESULTS:In all patients parenchymal contrast enhancement was visually detectable. One hundred thirty-one characteristic time-intensity curves (baseline phase, peak contrast intensity, slow washout phase) were demonstrable in 144 ROIs. In ROIc and ROId, characteristic contrast curves could be observed most frequently (68/72 examinations), whereas time-intensity curves in ROIa and ROIb could not be evaluated because of inadequate contrast enhancement in 9 of 72 examinations. Time to peak intensity varied between 20 and 52 cardiac cycles; in 1 patient it was 88 cardiac cycles. In all individuals AUCs and in 16 of 18 subjects peak intensity in ROIc and ROId showed a 2- to 10-fold increase compared with ROIa and ROIb. In no examination did AUC ratios show a >2-fold side difference irrespective of the ROI.CONCLUSIONS:The present study demonstrates for the first time that TRsHI produces accurate contrast in different brain areas and represents an ultrasonic tool related to brain perfusion. Absolute values of quantitative parameters show high variations caused by different temporal bone thicknesses and a complex relationship between echo contrast concentrations and measurements of optic intensities. Ratios between different ROIs help to compare contrast enhancement in different brain areas. Furthermore, because of the fact that attenuation of contrast enhancement in TRsHI depends strictly on the insonation depth, harmonic imaging studies of brain perfusion cannot be compared directly with other imaging techniques such as positron emission tomography.

Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B-2 and prostaglandin (PG)F-2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB(2) and PGF(2 alpha) measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.