Biomolecular Structure Prediction Stochastic Optimization Methods

Biomolecular structure prediction remains an important challenge to biophysical chemistry. We recently developed an all‐atom free energy forcefield (PFF01) for protein structure prediction with stochastic optimization methods. We review recent studies, which demonstrated all‐atom folding of several proteins and summarize recent progress for in‐silico high‐throughput screening strategies for rational drug design, which are also based on the use of stochastic optimization methods to determine the conformation of the receptor‐ligand complex.     

Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE)

A surveillance study of nosocomial blood stream infections [Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)] was conducted during a 14-month period in 1995 to 1996 in approximately 50 American medical centers. Among the 4725 blood stream infections, the etiologic agent was Enterobacter spp. in 230, Citrobacter freundii in 24, and Serratia marcescens in 65. The vast majority of these isolates (89%) had been sent to the University of Iowa including 198 Enterobacter spp. (46 Enterobacter aerogenes, 141 Enterobacter cloacae, 11 other Enterobacter spp.), 23 C. freundii, and 62 S. marcescens. Because these species are capable of producing Amp C beta-lactamase, we examined their susceptibility to 12 broad-spectrum antimicrobial agents. The frequency of resistance to ceftazidime and the molecular epidemiology of ceftazidime-resistant strains was also examined. Among the Enterobacter spp. and C. freundii isolates, resistance to third generation cephalosporins (ceftazidime, ceftriaxone) and broad-spectrum semisynthetic penicillins (piperacillin), with or without an enzyme inhibitor (piperacillin/tazobactam), was high, e.g., 35 to 50%. The S. marcescens isolates were quite susceptible to all agents tested. Both imipenem and cefepime were active against virtually all isolates tested including 84 stably derepressed Amp C-producing ceftazidime-resistant strains of Enterobacter spp. and C. freundii. The overall rank order of activity for the six best agents against these Amp C-producing strains was: imipenem (100% susceptible) > amikacin = cefepime (98.6%) > ciprofloxacin = gentamicin = ofloxacin (93.6 to 94.0%). Molecular typing studies of ceftazidime-resistant E. cloacae using an automated ribotyping system, as well as pulsed-field gel electrophoresis, indicated that although clonal spread of a single strain occurred in some of the medical centers, most of the episodes of bacteremia were caused by patient-unique strains. Control of these resistant organisms will require attention to microbiologic recognition of phenotypes, to infection control practices, and to limiting the overuse of certain extended spectrum beta-lactams.     

Green's function based simulation of the optical spectrum of multisection lasers

A new approach for the calculation of the optical spectrum of semiconductor lasers is presented. It is based on a solution of the inhomogeneous coupled wave equations using the Green's function method. The spontaneous emission is modeled by Langevin noise functions. In contrast to previous theories, lasers with gain-coupled distributed feedback sections are properly described. The theoretical model is used in a fitting procedure for parameter extraction.     

Bildungsmechanismen im Primärschlackegebiet des Hochofens

Neues Verfahren zur Herstellung von großen Wüstitkristallen. Erörterung der Reaktionen zwischen Wüstit und Kalk-Kieselsäure-Gemischen. Deutung des Bildungsmechanismus im Primärschlackegebiet durch Erläuterung des Aufbaus hohler Körper aus reduzierten Eisenoxiden in Eiszapfenformen.     

Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey

Zinc transporter-3 (ZnT-3), a member of a growing family of mammalian zinc transporters, is expressed in regions of the brain that are rich in histochemically reactive zinc (as revealed by the Timm's stain), including entorhinal cortex, amygdala, and hippocampus. ZnT-3 protein is most abundant in the zinc-enriched mossy fibers that project from the dentate granule cells to hilar and CA3 pyramidal neurons. We show here by electron microscopy that ZnT-3 decorates the membranes of all clear, small, round synaptic vesicles (SVs) in the mossy fiber boutons of both mouse and monkey. Furthermore, up to 60-80% of these SVs contain Timm's-stainable zinc. The coincidence of ZnT-3 on the membranes of SVs that accumulate zinc, and its homology with known zinc transporters, suggest that ZnT-3 is responsible for the transport of zinc into SVs, and hence for the ability of these neurons to release zinc upon excitation.     

Stoffaustausch zwischen flüssigem Eisen und Schlacke beim Sprühraffinationsverfahren

Erläuterung des Sprühraffinationsverfahrens, bei dem eine Schmelze mit inertem Gas verdüst wird und die entstehenden Metalltropfen durch eine Raffinationsschlacke fallen. Erörterung der Gesetzmäßigkeiten für die Stoffaustauschvorgänge zwischen Metalltropfen und Schlacke. Bestimmung der mittleren Tropfengröße beim Versprühen von kohlenstoffgesättigtem Roheisen. Untersuchung der Wirkung der Sprühraffination am Beispiel der Entschwefelung des Roheisens mit Schlacken des Systems CaO–CaF₂–Al₂O₃ bei 1600 °C. Ermittlung des Stoffübergangskoeffizienten des Schwefels für den umgekehrt transitorischen Phasenkontakt und Vergleich mit Werten bei anderen Techniken des Phasenkontaktes Metall-Schlacke.     

Association of secondary and polymicrobial nosocomial bloodstream infections with higher mortality

The objective of this study was to characterize microbiological factors independently associated with higher mortality rates following nosocomial bloodstream infection. All patients admitted to the University of Iowa Hospitals and Clinics between 1 July 1989 and 30 June 1990 who developed a nosocomial bloodstream infection were included. The crude in-house mortality for the 364 patients with nosocomial bloodstream infections was 33%. These deaths accounted for 25% of all in-hospital deaths. Significant risk factors for death from bloodstream infection included diagnoses of cancers and diseases of the cardiovascular and respiratory systems (p < 0.01). Neither previous surgery nor neutropenia was associated with higher mortality rates. Whereas the crude mortality rates associated with gram-negative (33%) and gram-positive (31%) bloodstream infections were similar, that associated with fungemia was higher (54%, p < 0.02). The mortality associated with secondary bloodstream infections (46%) was higher than that associated with primary bloodstream infections (28%, p < 0.001). Furthermore, polymicrobial infections had a worse prognosis than infections from which a single pathogen was isolated (p < 0.05). A multivariate, logistic regression model identified four variables that independently predicted mortality (p = 0.025): age (OR 1.01 per year; CI95 1.00-1.02); cancer (OR 2.35, CI95 1.26-4.37) or diseases of the cardiovascular or respiratory systems (OR 2.20, CI95 1.04-4.67); polymicrobial infection (OR 2.34; CI95 1.21-4.53); and secondary bloodstream infection (OR 2.46; CI95 1.50-4.02). The last variable was the strongest independent predictor. Our study demonstrates the importance of microbiological factors in the outcome of nosocomial bloodstream infections.