A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

Thermal-lens and photo-acoustic methods for the determination of SiC thermal properties

In this paper we report the use of photothermal techniques such as Thermal lens (TL) spectrometry, Photoacoustic and heat capacity, ρc_p, to determine the thermo-optical parameters, such as thermal conductivity (K), thermal diffusivity (D), specific heat (c_p) and the optical path dependence with temperature (ds/dT), of an undoped polycrystalline 3C-SiC. To our knowledge, this is the first time that Thermal lens technique is used for wide band-gap systems. Results obtained for the polycrystalline sample with TL technique indicates that ds/dT is negative at room temperature. Moreover, the obtained values of thermal diffusivity and thermal conductivity are in good agreement with that found in the literature, indicating that the phototermal techniques can be used to obtain the referred parameters in circumstances where other techniques cannot be used, for example, in harsh environments.     

Learning user preferences of route choice behaviour for adaptive route guidance

As the use of navigation systems becomes more widespread, the demand for advanced functions of navigation systems also increases. In the light of user satisfaction, personalisation of route guidance by incorporating user preferences is one of the most desired features. A user model applied to personalised route guidance is presented. The user model adaptively updates route selection rules when it discovers the predicted choice differs from the actual choice of the driver. This study employs a decision tree learning algorithm, the C4.5 algorithm, which has advantages over other data mining methods in terms of its comprehensible model structure. Simulation experiments with a real-world network were conducted to analyse the applicability of the model to adaptive route guidance and the accuracy of its prediction