a b b a s @ i s l . s t a n f o r d . e d u AbstractConventional methods for optimal sizing of wires and transistors use linear RC circuit models and the Elmore delay as a measure of signal delay. If the RC circuit has a tree topology the sizing problem reduces to a convex optimization problem which can be solved using geometric programming. The tree topology restriction precludes the use of these methods in several sizing problems of significant importance to highperformance deep submicron design including, for example, circuits with loops of resistors, e.g., clock distribution meshes, and circuits with coupling capacitors, e.g., buses with crosstalk between the lines. The paper proposes a new optimization method which can be used to address these problems. The method uses the dominant time constant as a measure of signal propagation delay in an RC circuit, instead of Elmore delay. Using this measure, sizing of any RC circuit can be cast as a convex optimization problem which can be solved using the recently developed efficient interior-point methods for semidefinite programming. The method is applied to two important sizing problems -sizing of clock meshes, and sizing of buses in the presence of crosstalk.

A total of 51 bacterial strains were isolated from fairy shrimps [Branchipus schaefferi (Fisher), Chirocephalus diaphanus (Prévost) and Streptocephalus torvicornis (Waga)] showing signs of 'black disease'. The fairy shrimps showed black nodules on the thoracic appendages, the cercopods, the antennae and sometimes at the back of the head. The infection sites on the thoracic appendages were restricted to the proximal parts of the endopodite, the exopodite and endite I. In order to check Koch's postulates, pure bacterial cultures were administered to healthy fairy shrimps. One bacterial pathogen was identified as Aeromonas hydrophila using BIOLOG and the genotypic fingerprinting technique AFLP.

The major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in ~50% of patients to recover a normal platelet count after anti-CD20 Rituximab-mediated B cell depletion and splenectomy suggest that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SC) reside in other anatomical compartments. We analyzed >3,300 single IgG-SC from spleen, bone marrow and/or blood of 27 patients with ITP revealing high inter-individual variability in affinity for GPIIbIIIa with variations over 3 logs. IgG-SC dissemination and range of affinities were however similar per patient. Longitudinal analysis of autoreactive IgG-SC upon treatment with anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti-GPIIbIIIa IgG-SC in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies.

It is difficult to measure karst volume but important to do so to assess risk of sinkhole formation. Measurements of airflow and atmospheric pressure pattern on a water well in buried karst of the overexploited Tournai hydrogeological basin (Belgium) show that inflow and outflow are highly correlated to atmospheric pressure and the differences of external and internal air densities. The volume of natural voids in connection with the well within the vadose zone can best be estimated by a calculation based on outflow under constant atmospheric pressure, which suggests a possible cavity volume of 700 000 m3 indicating likelihood of sinkhole formation.

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