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U Fischer

Publications and source records attributed to U Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Benchmarking of Monte Carlo based shutdown dose rate calculations for applications to JET.

The calculation of dose rates after shutdown is an important issue for operating nuclear reactors. A validated computational tool is needed for reliable dose rate calculations. In fusion reactors neutrons induce high levels of radioactivity and presumably high doses. The complex geometries of the devices require the use of sophisticated geometry modelling and computational tools for transport calculations. Simple rule of thumb laws do not always apply well. Two computational procedures have been developed recently and applied to fusion machines. Comparisons between the two methods showed some inherent discrepancies when applied to calculation for the ITER while good agreement was found for a 14 MeV point source neutron benchmark experiment. Further benchmarks were considered necessary to investigate in more detail the reasons for the different results in different cases. In this frame the application to the Joint European Torus JET machine has been considered as a useful benchmark exercise. In a first calculational benchmark with a representative D-T irradiation history of JET the two methods differed by no more than 25%. In another, more realistic benchmark exercise, which is the subject of this paper, the real irradiation history of D-T and D-D campaigns conducted at JET in 1997-98 were used to calculate the shut-down doses at different locations, irradiation and decay times. Experimental dose data recorded at JET for the same conditions offer the possibility to check the prediction capability of the calculations and thus show the applicability (and the constraints) of the procedures and data to the rather complex shutdown dose rate analysis of real fusion devices. Calculation results obtained by the two methods are reported below, comparison with experimental results give discrepancies ranging between 2 and 10. The reasons of that can be ascribed to the high uncertainty on the experimental data and the unsatisfactory JET model used in the calculation. A new dedicated JET benchmark experiment will be performed trying to solve these issues.

Algorithms↗
PubMed2005

Three-dimensional shielding calculations for the IFMIF neutron source using a coupled Monte Carlo/Deterministic computational scheme.

Shielding calculations for the International Fusion Materials Irradiation Facility (IFMIF) are complicated due to the geometrical complexity of the target system and the large-scale bulk shields around the source target. Three-dimensional shielding calculations were performed by using a newly developed Monte Carlo/Deterministic computational scheme. The neutron-photon fluxes and dose rate distributions in the back wall of the Test Cell and the access/maintenance room are presented and compared with previous shielding calculations. The results demonstrate that this coupled scheme is an useful computational tool for three-dimensional shielding analyses of complex and large nuclear facilities.

Computer Simulation↗
PubMed2005

Ischaemic stroke in young adults: predictors of outcome and recurrence.

BACKGROUND: There is limited information about predictors of outcome and recurrence of ischaemic stroke affecting young adults. OBJECTIVE: To assess the predictive value of the presenting characteristics for both outcome and recurrence in young stroke victims. METHODS: Clinical and radiological data for 203 patients aged 16 to 45 years were collected prospectively; they comprised 11% of 1809 consecutive patients with ischaemic stroke. The National Institutes of Health stroke scale (NIHSS), the Bamford criteria, and the trial of ORG 10172 in acute stroke treatment (TOAST) classification were used to define stroke severity, subtype, and aetiology. The clinical outcome of 198 patients (98%) was assessed using the modified Rankin scale (mRS) and categorised as favourable (score 0-1) or unfavourable (score 2-6). RESULTS: Stroke was caused by atherosclerotic large artery disease in 4%, cardioembolism in 24%, small vessel disease in 9%, another determined aetiology in 30%, and undetermined aetiology in 33%. Clinical outcome at three months was favourable in 68%, unfavourable in 29%, and lethal in 3%. Thirteen non-fatal stroke, two fatal strokes, and six transient ischaemic attacks (TIA) occurred during a mean (SD) follow up of 26 (17) months. High NIHSS score, total anterior circulation stroke, and diabetes mellitus were independent predictors of unfavourable outcome or death (p<0.0001, p = 0.011, and p = 0.023). History of TIA predicted stroke recurrence (p = 0.02). CONCLUSIONS: Severe neurological deficits at presentation, total anterior circulation stroke, and diabetes mellitus predict unfavourable outcome. Previous TIA are associated with increased risk of recurrence.

Adolescent↗
PubMed2005

Recanalisation of middle cerebral artery occlusion after intra-arterial thrombolysis: different recanalisation grading systems and clinical functional outcome.

BACKGROUND: Different grading systems of arterial recanalisation have never been compared in large series of stroke patients treated with intra-arterial thrombolysis (IAT). METHODS: Clinical and angiographic findings and outcome were analysed in 147 patients with M1 or M2 segment occlusion of the middle cerebral artery treated with IAT. Associations of the thrombolysis in myocardial infarction (TIMI) grading system and the Mori grading system with clinical outcome were compared. RESULTS: The median NIHSS score on admission was 15 and the mean time from symptom onset to IAT was 242 minutes. After three months the outcome was favourable (defined as modified Rankin scale score (mRS) < or = 2) in 85 patients (58%) and poor (mRS 3 to 5) in 44 (30%); 18 patients (12%) were dead. Recanalisation was categorised as TIMI grade 0 in 17 patients (12%), TIMI 1 in 16 (11%), TIMI 2 in 83 (56%), and TIMI 3 in 31(21%). Seventeen patients (12%) showed Mori grade 0 reperfusion, 16 (11%) Mori 1, 37 (25%) Mori 2, 46 (31%) Mori 3, and 31 (21%) Mori 4. In both TIMI and Mori grading systems, reopening the artery was an independent predictor of a favourable clinical outcome (p < 0.0001). When recanalisation was partial, outcome was better in patients with reperfusion >50% (Mori 3) than in those with reperfusion <50% (Mori 2) (p = 0.008). CONCLUSIONS: Both TIMI and Mori grading systems are useful for predicting outcome after stroke and IAT. When recanalisation is partial the Mori classification is more refined in giving prognostic information.

Adolescent↗
PubMed2004

Proliferation and differentiation of osteoblasts on Biocement D modified with collagen type I and citric acid.

In this study, the proliferation and differentiation of rat calvarial osteoblasts cultured on either (1) calcium-phosphate bone cement Biocement D, (2) Biocement D with 2.5% (w/w) mineralized collagen type I, or (3) Biocement D with 2.5% (w/w) mineralized collagen type I and 3% (w/w) citric acid were investigated. Incubation of the composites in cell-culture medium resulted in a fast decrease of pH and calcium concentration as well as in an increase of phosphate concentration. Although these effects occurred with all investigated materials, the lowest extent could be observed for the citric-acid-containing composites. As shown by scanning-electron microscopy, osteoblasts adhered to the composite surfaces. Proliferation and differentiation of the cells grown on the composites were found to be reduced compared to cells grown on tissue-culture polystyrene. Cells cultured in the vicinity of the composites but without direct contact also exhibited a reduced rate of proliferation, reduced alkaline phosphatase activity, and reduced mineralization. Simulating the changes in calcium and phosphate concentration occasioned by the composites through exposing cells to EGTA and phosphate gives rise to the same effects of reducing proliferation, ALP activity, and mineralization. No indication for apoptosis in cells exposed to low calcium and high phosphate concentrations was found. The number of necrotic cells, however, increased after incubation with EGTA and phosphate. For assessment of cell-composite interactions and the success of the composites in vivo, as well as for more effective material development, it seems to be important to know how changes in microenvironmental pH and ion composition of the material affect cellular proliferation and differentiation.

Animals↗
PubMed2004

Potential involvement of rainbow trout thrombocytes in immune functions: a study using a panel of monoclonal antibodies and RT-PCR.

The functional relationship between fish and mammalian thrombocytes is relatively unknown. In this study, a panel of monoclonal antibodies (mAbs) was used to investigate the functional properties of rainbow trout thrombocytes. The mAbs recognize cell-surface molecules on thrombocytes with molecular weights ranging from 17 to 160 kDa. Flow cytometric and immuno-electron microscopic analyses demonstrate that these molecules are expressed at different levels and that surface expression increased upon activation with bovine collagen. Two of these cell-surface molecules (17 and 21 kDa) were directly involved in collagen-induced aggregation of thrombocytes since aggregation was blocked upon pre-treatment with mAbs that recognize the two surface markers. Interestingly, the percentage of thrombocytes in blood increased after stimulation using different antigens. The transcriptional profile of trout thrombocytes was then examined after immuno-magnetic enrichment using the described mAbs to assess potential roles of trout thrombocytes in immune functions. Trout thrombocytes express components of the MHC class Ia pathway, IL1beta, TNFalpha, TGFbeta, the interleukin receptor common gamma chain as well as CXC and CC chemokines. MHC class IIB and TNFalpha were expressed at low levels in resting thrombocytes. No evidence was found for the expression of TCRalphabeta, Ig heavy chain, CD8alpha or CK1 mRNA. Taken together, these results suggest that rainbow trout thrombocytes express molecules involved in activation, aggregation and genes encoding proteins, that are involved in antigen presentation and immune regulation.

Animals↗
PubMed2004

Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus.

Interspecific hybridization in the rodent genera Peromyscus and Mus results in abnormal placentation. In the Peromyscus interspecies hybrids, abnormal allelic interaction between an X-linked locus and the imprinted paternally expressed Peg3 locus was shown to cause the placental defects. In addition, loss-of-imprinting (LOI) of Peg3 was positively correlated with increased placental size. As in extreme cases this placental dysplasia constitutes a post-zygotic barrier against interspecies hybridization, this finding was the first direct proof that imprinted genes may be important in speciation and thus in evolution. In the Mus interspecies hybrids, a strong role of an X-linked locus in placental dysplasia has also been detected. However, here we show by backcross and allele specific expression analyses that neither LOI of Peg3 nor abnormal interactions between Peg3 and an X-linked locus are involved in generating placental dysplasia in Mus hybrids, although the placental phenotypes observed in the two genera seem to be identical. In contrast to this, another dysgenesis effect common to Peromyscus and Mus hybrids, altered foetal growth, is caused at least in part by the same X-chromosomal regions in both genera. These findings first underline the strong involvement of the X-chromosome in the genetics of speciation. Secondly, they indicate that disruption of epigenetic states, such as LOI, at specific loci may be involved in hybrid dysgenesis effects in one group, but not in another. Thus, we conclude that even in closely related groups divergent molecular mechanisms may be involved in the production of phenotypically similar post-zygotic barriers against hybridization.

Alleles↗
PubMed2003

[Mammography].

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Adult↗
PubMed2003

Amino acid sequences and distribution of high-potential iron-sulfur proteins that donate electrons to the photosynthetic reaction center in phototropic proteobacteria.

High-potential iron-sulfur protein (HiPIP) has recently been shown to function as a soluble mediator in photosynthetic electron transfer between the cytochrome bc1 complex and the reaction-center bacteriochlorophyll in some species of phototrophic proteobacteria, a role traditionally assigned to cytochrome c2. For those species that produce more than one high-potential electron carrier, it is unclear which protein functions in cyclic electron transfer and what characteristics determine reactivity. To establish how widespread the phenomenon of multiple electron donors might be, we have studied the electron transfer protein composition of a number of phototrophic proteobacterial species. Based upon the distribution of electron transfer proteins alone, we found that HiPIP is likely to be the electron carrier of choice in the purple sulfur bacteria in the families Chromatiaceae and Ectothiorhodospiraceae, but the majority of purple nonsulfur bacteria are likely to utilize cytochrome c2. We have identified several new species of phototrophic proteobacteria that may use HiPIP as electron donor and a few that may use cytochromes c other than c2. We have determined the amino acid sequences of 14 new HiPIPs and have compared their structures. There is a minimum of three sequence categories of HiPIP based upon major insertions and deletions which approximate the three families of phototrophic proteobacteria and each of them can be further subdivided prior to construction of a phylogenetic tree. The comparison of relationships based upon HiPIP and RNA revealed several discrepancies.

Amino Acid Sequence↗
PubMed2003

Transforming growth factor beta1 immobilized adsorptively on Ti6Al4V and collagen type I coated Ti6Al4V maintains its biological activity.

Titanium and titanium alloys are often used for orthopedic and dental implants. Osseointegration of Ti6Al4V may be improved not only by precoating of the surface with extracellular matrix proteins like collagen type I but also by additional immobilization of growth factors. In the present study, transforming growth factor beta1 (TGF-beta1) which is known as an inducer of collagen synthesis was immobilized adsorptively on uncoated and collagen type I coated Ti6Al4V surfaces. TGF-beta1 was found immobilized slightly faster to collagen type I coated than to uncoated Ti6Al4V and released slower from the collagen coated material. Immobilized TGF-beta1 is biologically active for at least 3 weeks storage at 4 degrees C. Sterilization by ethylene oxide inactivates immobilized TGF-beta1. In osteoblasts cultured on implants with adsorptively immobilized TGF-beta1, mRNA level and specific catalytic activity of alkaline phosphatase as well as accumulation of calcium and phosphate were found reduced, whereas procollagen alpha1(I) mRNA level and the rate of collagen synthesis were increased.

Adsorption↗
PubMed2003

Many cuts to ruin: a comprehensive update of caspase substrates.

Apoptotic cell death is executed by the caspase-mediated cleavage of various vital proteins. Elucidating the consequences of this endoproteolytic cleavage is crucial for our understanding of cell death and other biological processes. Many caspase substrates are just cleaved as bystanders, because they happen to contain a caspase cleavage site in their sequence. Several targets, however, have a discrete function in propagation of the cell death process. Many structural and regulatory proteins are inactivated by caspases, while other substrates can be activated. In most cases, the consequences of this gain-of-function are poorly understood. Caspase substrates can regulate the key morphological changes in apoptosis. Several caspase substrates also act as transducers and amplifiers that determine the apoptotic threshold and cell fate. This review summarizes the known caspase substrates comprising a bewildering list of more than 280 different proteins. We highlight some recent aspects inferred by the cleavage of certain proteins in apoptosis. We also discuss emerging themes of caspase cleavage in other forms of cell death and, in particular, in apparently unrelated processes, such as cell cycle regulation and cellular differentiation.

Animals↗
PubMed2002

Computer-aided detection in direct digital full-field mammography: initial results.

For the first time, full-field digital mammography (FFDM) allows computer-aided detection (CAD) analysis of directly acquired digital image data. The purpose of this study was to evaluate a CAD system in patients with histologically correlated breast cancer depicted with FFDM. Sixty-three cases of histologically proven breast cancer detected with FFDM (Senographe 2000D, GE Medical Systems, Buc, France) were analyzed using a CAD system (Image Checker V2.3, R2 Technology, Los Altos, Calif.). Fourteen of these malignancies were characterized as microcalcifications, 37 as masses, and 12 as both. The mammographic findings were categorized as BI-RADS 3 (n=5), BI-RADS 4 (n=17) and BI-RADS 5 (n=40). The sensitivity for malignant lesions and the rate of false-positive marks per image were calculated. The sensitivity and its 95% confidence interval (CI) were estimated. The sensitivity of the CAD R2 system in breast cancer seen on FFDM was 89% for microcalcifications [CI(95%)=(70%; 98%)] and 81% for masses [CI(95%)=(67%; 91%)]. As expected, the detection rate was higher in lesions categorized as BI-RADS 5 (37 of 40) compared with lesions categorized as BI-RADS 4 (11 of 17). In the group categorized as BI-RADS 3 the detection rate was 4 of 5 lesions; however, this group was very small. The rate of false-positive marks was 0.35 microcalcification marks/image and 0.26 mass marks/image. The overall rate of false-positive marks was 0.61 per image. CAD based on FFDM provides an optimized work flow. Results are equivalent to the results reported for CAD analysis of secondarily digitized image data. Sensitivity for microcalcifications is acceptable and for masses is low. The number of false-positive marks per image should be reduced.

Breast Neoplasms↗
PubMed2002

Evaluation of immune functions of rainbow trout (Oncorhynchus mykiss)--how can environmental influences be detected?

In fish, the first line of defense against infectious microorganisms is based on a broad range of nonspecific humoral and cellular immune mechanisms ("innate immunity") which without prior specific activation can act in forming a more static barrier (Fish Shellfish Immunol. 10 (2000) 243; Dev. Comp. Immunol. 25 (2001) 827). This natural resistance is normally effective enough to protect fish from infectious diseases until specific immune responses are being induced (Fig. 1; Dev. Comp. Immunol. 25 (2001) 841). Healthy fish exhibit both nonspecific and specific immune responses depending directly on environmental temperature. Pollution of the natural aquatic environment with industrial or agricultural sewage is an important immunosuppressing factor resulting in higher susceptibility to infectious diseases. To date, the possible immunotoxicity of a substance is evaluated using quantification of humoral factors like lysozyme, complement, C-reactive protein or total immunoglobulins but less often using functional assays. Furthermore, most of the functional assays (phagocytosis, respiratory burst, proliferative response) are based on the measurement of the response of resting but not of specific activated immune cells. However, the physiological responses of the immune system to an infection are based on a complex, stepwise activation and proliferation, especially of the specific immune functions after first contact to the microorganisms. In this report we describe in vitro methods for the evaluation of cellular immune functions of different leukocyte populations after specific in vivo triggering of the immune system. Parameters to be evaluated are activation and proliferation of leukocyte populations, phagocytosis and respiratory burst, secretion of antigen-specific antibodies and specific cell-mediated cytotoxicity. Furthermore, challenge models with bacterial (Aeromonas salmonicida) and viral pathogens (Viral Haemorrhagic Septicemia Virus, VHSV) are presented.

Animals↗
PubMed2002

Comparative study in patients with microcalcifications: full-field digital mammography vs screen-film mammography.

The goal of this prospective study was to compare a full-field digital mammography system (FFDM) to a conventional screen-film mammography system (SFM) for the detection and characterization of microcalcifications. Fifty-five patients with 57 isolated microcalcification clusters were examined using a FFDM system (Senographe 2000D, GE Medical Systems, Milwaukee, Wis.) and a SFM system (Senographe DMR, GE Medical Systems, Milwaukee, Wis.). A conventional screen-film mammogram and a digital contact mammogram were obtained of each cluster. The image quality and the number of calcification particles were evaluated, and a characterization (BI-RADS 1-5) of microcalcifications was given by four experienced readers. Histopathology revealed 16 benign lesions (sclerosing adenosis, dysplasia, hamartoma, radial scar) in 15 patients and 21 malignant tumors (in situ carcinoma, invasive carcinoma) in 20 patients. Twenty patients had benign changes verified by long-term follow-up. Image quality of FFDM was assessed as superior to SFM in more than 50% of the cases. The FFDM showed more calcifications in 41% of all cases. Sensitivity and specificity for FFDM vs SFM were 95.2 vs 91.9% and 41.4 vs 39.3%, respectively. Moreover, FFDM demonstrated a higher diagnostic accuracy (deviation: 0.86 BI-RADS steps) compared with FSM (deviation 0.93 BI-RADS steps). The FFDM system with a 100- micro m pixel size provides better image quality than SFM in patients with mammographic microcalcifications. The FFDM has a higher sensitivity and a higher reliability in characterizing microcalcifications.

Breast Neoplasms↗
PubMed2002

Classification of hypervascularized lesions in CE MR imaging of the breast.

The purpose of this paper is to define and evaluate a classification category for contrast-enhanced (CE) MR imaging of the breast based on the BI-RADS mammographic categories of the American College of Radiology. Using five evaluation criteria for MR findings (initial signal increase, post-initial signal behavior, shape, border, and contrast material distribution within enhancing tumors) 522 patients (1031 breasts) were analyzed. Scores were given from 0 to 8 points and classified into five categories (group I: 0 points, negative; group II: 1-2 points, benign; group III: 3 points, probably benign; group IV: 4-5 points, suspicious abnormality; group V: 6-8 points, highly suspicious for malignancy) to 265 focal hypervascularized breast lesions in 244 breasts (patient group A). These findings were correlated with histology or follow-up. Additionally, this classification was correlated to the contrast medium uptake within the parenchyma of the remaining 787 breasts without any focal lesion (patient group B). Two hundred sixty-five hypervascularized lesions in 238 patients (244 breasts, patient group A) were classified into group I: 0%; group II: 27.3%; group III: 22.3%; group IV: 18.6%; and group V: 31.8%. Histology revealed 115 benign and 134 malignant tumors in these groups. Sixteen benign lesions were controlled by follow-up. Sensitivity for the detection of malignancy using the presented multifactorial MRM classification was 92%, and specificity was 92%. Excluding cases of ductal carcinoma in situ specificity increased to 95%. Seven hundred eighty-seven breasts without any focal hypervascularized lesion (patient group B) were classified into groups I or II. Follow-up ( n=771) or histology ( n=14) confirmed the diagnosis in 785 of these breasts. Histopathology revealed, however, malignant tumors in the remaining two cases. The classification of lesions based on a multifactorial analysis is very helpful in the interpretation of CE MRI of the breast. The evaluation of all diagnostic imaging modalities, however, is essential in determining the correct diagnosis and/or in deciding on the appropriate therapeutic procedure.

Breast↗
PubMed2002

18F-FDG hybrid PET in patients with suspected spondylitis.

This study investigated the value of fluorine-18 2'-deoxy-2-fluoro- D-glucose (FDG) imaging with a double-headed gamma camera operated in coincidence (hybrid PET) detection mode in patients with suspected spondylitis. Comparison was made with conventional nuclear medicine imaging modalities and magnetic resonance imaging (MRI). Sixteen patients with suspected spondylitis (nine male, seven female, mean age 59 years) prospectively underwent FDG hybrid PET (296 MBq) and MRI. For intra-individual comparison, the patients were also imaged with technetium-99m methylene diphosphonate (MDP) (555 MBq) ( n=13) and/or gallium-67 citrate (185 MBq) ( n=11). For FDG hybrid PET, two or three transverse scans were performed. Ratios of infected (target) to non-infected (background) (T/B) vertebral bodies were calculated. MR images were obtained of the region of interest. Patients found positive for spondylitis with MRI and/or FDG hybrid PET underwent surgical intervention and histological grading of the individual infected foci. Twelve out of 16 patients were found to be positive for spondylitis. Independent of the grade of infection and the location in the spine, all known infected vertebrae ( n=23, 9 thoracic, 12 lumbar, 2 sacral) were detected by FDG hybrid PET. T/B ratios higher than 1.45+/-0.05 (at 1 h p.i.) were indicative of infectious disease, whereas ratios below this value were found in cases of degenerative change. FDG hybrid PET was superior to MRI in patients who had a history of surgery and suffered from a high-grade infection in combination with paravertebral abscess formation ( n=2; further computed tomography was needed) and in those with low-grade spondylitis ( n=2, no oedema) or discitis ( n=2, mild oedema). False-positive 67Ga citrate images ( n=5: 2 spondylodiscitis, 1 aortitis, 1 pleuritis, 1 pulmonary tuberculosis) and 99mTc-MDP SPET ( n=4: 1 osteoporosis, 2 spondylodiscitis, 1 fracture) were equally well detected by FDG hybrid PET and MRI. No diagnostic problems were seen in the other patients ( n=5). In this study, FDG hybrid PET was superior to MRI, 67Ga citrate and (99m)Tc-MDP, especially in patients with low-grade spondylitis (as compared with MRI), adjacent soft tissue infections (as compared with 67Ga citrate) and advanced bone degeneration (as compared with 99mTc-MDP).

Adult↗
PubMed2002

Cell surface trafficking of Fas in NIT-1 cells and dissection of surface and total Fas expression.

The appearance of Fas receptor at the surface of pancreatic beta-cells affected by progressive insulitis strongly suggests that Fas-mediated beta-cell apoptosis plays an important role in the pathogenesis of type 1 diabetes. In support of this concept, the present study has shown that islet cells from NOD mice and the beta-cell line NIT-1 respond to the proinflammatory cytokines IL-1beta and IFN-gamma with Fas surface expression in a dose- and time-dependent manner. Moreover, the prevention of cytokine-induced surface Fas expression by actinomycin D, cycloheximide, and brefeldin A demonstrated that trafficking of Fas to the beta-cell surface requires RNA and protein synthesis and, in addition is critically dependent on intracellular protein transport. Compared with total cellular Fas protein, the amount of Fas at the cell surface was relatively small and indicated that Fas is preferentially expressed in cytoplasmic compartments of NIT-1 cells. It is concluded that inflammatory insults specifically induce translocation of Fas to the beta-cell surface and that interference with cell surface Fas expression is a new strategy to improve beta-cell survival in inflamed islets.

Animals↗