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Fur den Entwurf und die Analyse von integrierten Schaltungen werden geeignete Modelle der einzelnen Bauelemente benotigt. Detaillierte Modelle werden fur genaue Simulationen von kleinen Schaltungen eingesetzt, wahrend einfache Modelle fur die Simulationen von hochkomplexen Schaltungen verwendet werden. Da das benutzte Modell die Genauigkeit der Schaltungsanalyse festlegt, mus der Entwickler von integrierten Schaltungen uber Kenntnisse der gewohnlich benutzten Modelle verfugen. Dazu gehort das Verstandnis der zur Modellbildung notwendigen Annahmen und Naherungen sowie der daraus folgenden Grenzen fur die Anwendbarkeit der jeweiligen Modelle.

Study objectives: Different b-agonists are compared with regard to their cardiodepressive side effects. Design: The metaphenolic bronchodilators reproterol, salbutamol, fenoterol, and terbutaline were introduced at a dosage of 0.0005 mmol to a maximum of 10 mmol per gram of heart tissue into the isolated working rat heart under hypoxic conditions, and the response was observed during subsequent reoxygenation. As an index of external heart work, aortic flow was measured. Heart rate, coronary flow, and developed pressure were recorded. At the end of heart perfusion, mitochondria were isolated and analyzed for adenosine triphosphatase activity, adenosine triphosphate (ATP) synthesis, and membrane fluidity. Moreover, intact mitochondria and lipid peroxidation were investigated using a model system. Measurements and results: Compared to controls, reproterol gave the most favorable results, with an increase of 25 to 30% of aortic flow during reoxygenation at a concentration of 10 mmol/g heart tissue. In contrast, both fenoterol and salbutamol at a concentration of 1 mmol/g heart tissue decreased aortic flow during reoxygenation, whereas terbutaline had a negative influence on aortic flow at 0.01 to 0.1 mmol/g heart tissue. Mitochondria of these hearts were isolated at the end of the experiment. Mitochondrial ATP synthesis was increased above controls at nearly all concentrations of reproterol. ATP synthesis was decreased at 1 mmol and 10 mmol fenoterol. As little as 0.0005 mmol terbutaline decreased ATP synthesis by 50%. In intact mitochondria, adenosine diphosphate (ADP) to oxygen ratios were found to be increased with terbutaline and fenoterol, indicating ADP consumption by myokinase activation. Lipid peroxidation was increased in a model system between concentrations of 0.002 mmol/mg and 0.04 mmol/mg phosphatidylcholine by fenoterol and terbutaline, whereas a decrease was noted with reproterol. Membrane fluidity was found increased after addition of reproterol, which supports the evidence of efficient ATP synthesis by this compound. Conclusions: Cardiodepressive side effects and greater toxicity of fenoterol and terbutaline were found under the conditions of our experiment. Salbutamol and, in particular, reproterol appear much better tolerated. In addition to partial b-adrenergic agonism, reproterol may exert an inhibitory influence on adenosine receptor sites and phosphodiesterase, which could result in membrane stabilization by saving cyclic adenosine monophosphate or ATP. (CHEST 2000; 117:519‐529)

Basophils and mast cells play a crucial role in immunological and allergic processes due to the release of inflammatory mediators such as histamine. It has been suggested for a long time that the hist

Recent studies have shown that human basophils, like mast cells, generate interleukin (IL)-4 following immunological activation and may thus participate in late-phase allergic and inflammatory processes. Here, we report the capacity of human basophils to release IL-13 within 24 h following stimulation with anti-IgE. Additionally, in 14 out of 31 experiments, we observed that basophils rapidly release performed IL-4 within 5-10 min, as well as newly generated IL-4, which was released 4 h following stimulation of the cells with anti-IgE. In contrast to the biphasic release of IL-4 from the cells, no preformed IL-13 was detected at earlier times (5-30 min). Preformed IL-4 and IL-4 and IL-13 generated de novo were also released after stimulation of the cells with IL-3; an enhanced production of these cytokines was observed using a combination of IL-3 and anti-IgE. We conclude from these data that, by releasing performed IL-4 and IL-4 and IL-13 generated de novo, human basophils may be centrally involved in the orchestration of allergic inflammation by providing a trigger to IL-4-mediated T helper 2 lymphocyte activation, B cell IgE switching, and increased vascular adhesion molecule expression.

Carry-save arithmetic, well known from multiplier architectures, can be used for the efficient CMOS implementation of a much wider variety of algorithms for high-speed digital signal processing than, only multiplication. Existing architectural strategies and circuit concepts for the realization of inner-product based and recursive algorithms are recalled. The two's complement overflow behavior of carry-save arithmetic is analyzed and efficient overflow correction schemes are given. Efficient approaches are presented for the carry-save, implementation of a saturation control. The concepts are extended and refined for the high-throughput implementation of decisiondirected algorithms such as division, modulo multiplication and CORDIC which have yet been avoided because of a lack of efficient concepts for implementation.

Objective and Design: We report a method for basophil purification from buffy coats, which avoids positive selection of the cells and gives rise to good purity, yield and functional integrity of the cells.¶Subjects: Buffy coat blood (concentrated leukocyte fraction derived from 450 ml venipuncture donations) obtained from healthy blood donors (n = 51).¶Methods: Basophils were enriched by a three-step process starting with Ficoll density centrifugation (1.6 ± 0.1% basophil purity) followed by counter current centrifugal elutriation (17.7 ± 1.4% basophil purity). The final stage involved negative selection using Dynal immunomagnetic beads directed against CD2, CD14, CD16 and CD19 positive cell contaminants. Functional integrity of which was assessed by comparing the anti-IgE or calcium ionophore A23187 induced histamine release from basophils obtained from each enrichment step. Furthermore, basophil morphology was investigated using light and electron microscopy.¶Results: The final mean basophil purity of 67.3 ± 1.4% with a yield of 3.5 ± 0.5 × 106 basophils and a recovery of 21.8 ± 2.4% was achieved. Net histamine release from basophils stimulated with optimal concentrations of anti-human IgE was 39.1 ± 6.5% after Ficoll centrifugation, 41.6 ± 7.7% following elutriation and 35.7 ± 6.8% from the final purified fraction. Additionally, basophils enriched with our method showed intact morphology by electron microscopy and were functionally active to non-immunological stimulation.¶Conclusions: These results compare favourably with previous studies, which have often required the use of positive selection via the Fc RI receptor, which may result in cell degranulation, or cell sorting, which cannot be applied to large cell numbers. Our method provides a reproducible technique for basophil enrichment when large numbers of functionally intact basophils are required.

The elevated interleukin (IL)-4 and IgE production in Schistosoma mansoni infection seems to be induced essentially by the egg stage of the parasite. The underlying mechanism, however, is not known. Since basophils from human peripheral blood can produce IL-4, we asked, whether soluble S. mansoni egg antigens (SEA) would trigger basophils to release IL-4. Basophils from healthy human donors (n = 32) without prior history of schistosomiasis were incubated with SEA in the presence of IL-3. In all donors, IL-4 was produced at different concentrations. The IL-4 production was dependent on the dose of SEA, was correlated with the purity of the basophil preparation, and the IL-4 concentration in the culture supernatant was maximal 5 h after stimulation with SEA. In addition to its IL-4-stimulatory effect, SEA triggered basophils to degranulate, thereby releasing histamine and sulfidoleukotrienes. Stripping of receptor-bound IgE from basophils inhibited both SEA- and anti-IgE-induced, but not ionomycin-induced IL-4 production. Moreover, resensitization of stripped basophils with stripping supernatants or human serum restored SEA-induced IL-4 production. This suggests that IgE is involved in the mechanism of IL-4 induction by SEA. Since IL-4 is induced in basophils from nonexposed donors, basophils may play a role as an early source of IL-4 in S. mansoni infection.

We propose a radix-r digit-recurrence algorithm for complex square-root. The operand is prescaled to allow the selection of square-root digits by rounding of the residual. This leads to a simple hardware implementation. Moreover, the use of digit recurrence approach allows correct rounding of the result. The algorithm, compatible with the complex division, and its design are described at a high-level. We also give rough comparisons of its latency and cost with respect to implementation based on standard floating-point instructions as used in software routines for complex square root.; Nous proposons un algorithme itératif de racine carrée de base r. L’opérande est préalablement mise à l’échelle afin de permettre une sélection élémentaire des chiffres du résultat. Ceci permet une implantation matérielle simple. De plus, l’algorithme autorise un arrondi correct du résultat. Nous décrivons cet algorithme (compatible avec un algorithme de division complexe que nous avons proposé auparavant) à un haut niveau, et donnons des estimations grossière de son délai et de son coût, afin de le comparer à des algorithmes utilisant des instructions virgule flottante conventionnelles