Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.     

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.     

Methodological issues in outcome studies of school-based interventions for the prevention of adolescent depression.

Several methodological and ethical issues are addressed in the context of 3 related school-based studies of the primary and targeted prevention of depressive symptoms and disorder in high school adolescents. These issues include obtaining S consent and the protection of confidentiality, minimizing attrition over long-term follow-up periods, the "unit of assignment" issue common to most school-based research, and ensuring therapist fidelity to the intervention protocol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Driver detection and recognition of lineside signals and signs at different approach speeds

A study was carried out using simulation to investigate driver responses to lineside signals and signs at various approach speeds. The objectives of the study were: (1) to find out whether train speed would significantly affect signal/sign reading; (2) to examine at which point certain types of signs or signals could be detected or recognised, and (3) to determine a speed cut-off level above which certain types of signs or signals are no longer recognisable or detectable. Fifty-seven train drivers from 12 Train Operating Companies in the UK participated in the trials. Twenty different types of lineside signs and ten types of signals were tested under six different approach speeds ranging from 100 to 350 km/h (62–218 mph). Driver performance measures were ‘time remaining to the signal/sign’ at the point of detection or recognition, and reading error rate. The results showed a significant influence of train speed on driver responses to lineside signals/signs and demonstrated a non-linear relationship between driver responses to signals/signs and approach speed. This has been used to estimate a maximum approach speed limit within which a specific signal or sign can be correctly detected or recognised. The findings and implications of the study are discussed in the paper.     

Summary of discussion on ‘Sciences related to pitch and coke usage in carbon manufacture’

This article is a brief summary of the Discussion session held after the presentation of the preceding papers at the conference organized by the Industrial Carbon and Graphite Group of the Society of Chemical Industry, London, March 1984.