Computer-aided design of chiral ligands. Part I. Database search methods to identify chiral ligand types for asymmetric reactions

The utility of database searching to identify chiral ligand motifs is outlined. The key elements of three known chiral ligands have been described as bond vectors. The CAVEAT program was then used to screen the Cambridge Structural Database (CSD), portions of the Chemical Abstracts Services three-dimensional database (CAS-3D), and the TRIAD tricyclic structure database for scaffolds containing these elements. Scaffolds corresponding to the known starting points were identified indicating that this method can be used to identify chiral ligand structural motifs. In addition, alternate structural motifs were found that suggested alternative possible ligands.     

Effect of conventional and microwave sintering on the properties of yttria alumina garnet-dispersed austenitic stainless steel

The current study examines the effect of heating mode, temperature, and varying yttria alumina garnet (YAG) addition (5 and 10 wt pct) on the densification and properties of austenitic (316L) stainless steel. The straight 316L stainless steel and 316L-YAG composites were heated in a radiatively heated (conventional) and 2.45 GHz microwave sintering furnace. The compacts were consolidated through solid state as well as supersolidus sintering at 1200 °C and 1400 °C, respectively. Both 316L and 316L-YAG compacts couple with microwaves and heat to the sintering temperature rapidly (∼45 °C/min). The overall processing time was reduced by about 90 pct through microwave sintering. As compared to conventional sintering, compacts sintered in microwaves exhibit higher densification and finer microstructure but no corresponding improvement in mechanical properties and wear resistance. This has been correlated to elongated, irregular pore structure in microwave-sintered compacts.     

FECOM: a new artificial stool for evaluating defecation

OBJECTIVE: Traditionally, barium paste has been used for performing defecography. Because this substance is not stool-like, barium defecography may not accurately represent defecatory function. Our aim was to prospectively compare the utility of a new artificial stool, "FECOM"--a silicon-filled and barium-coated, deformable device the shape and consistency of which mimicked a normal formed stool with that of barium paste. METHODS: Defecography was performed after placing FECOM or barium paste in a random order in 12 healthy subjects (two men and 10 women). We evaluated the changes in anorectal angle, rectal morphology, rectal sensation, and the subjects' preference for a "stool-like" device. RESULTS: Anorectal angle at rest, during squeeze, cough, and straining were each greater with the FECOM when compared with the barium paste (p < 0.006). Anterior rectocele (nine), mucosal intussusception (four), and incontinence (three) were identified only with barium defecography. Nine (75%) subjects preferred FECOM to barium paste (p < 0.001) and reported that expulsion of this device mimicked more closely their stools at home (p < 0.05). CONCLUSION: The anorectal angle is influenced by the form and consistency of stool material and is lower with barium paste. The detection of rectocele, mucosal intussusception, and barium leakage in normal subjects during barium defecography questions the significance of these findings. FECOM appears to be a realistic alternative to barium paste for performing defecography.     

Waterfalls and geysers: the development of diversity awareness at Children's Hospital

The development of diversity awareness at Children's Hospital in Columbus, Ohio, has been a work in progress since the early 1980s. The interface of administration and individual initiatives ("waterfalls" and "geysers") has resulted in projects ranging from major international exchange programs to noontime Spanish language classes. This article recounts the journey from a parochial focus to a consciousness of multiculturalism in virtually all aspects of hospital interaction.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Ex vivo and in vitro testis and ovary explants: utility for identifying steroid biosynthesis inhibitors and comparison to a Tier I screening battery

Retinal ganglion cell (RGC) axons in lizards (reptiles) were found to regenerate after optic nerve injury. To determine whether regeneration occurs because the visual pathway has growth-supporting glia cells or whether RGC axons regrow despite the presence of neurite growth-inhibitory components, the substrate properties of lizard optic nerve myelin and of oligodendrocytes were analyzed in vitro, using rat dorsal root ganglion (DRG) neurons. In addition, the response of lizard RGC axons upon contact with rat and reptilian oligodendrocytes or with myelin proteins from the mammalian central nervous system (CNS) was monitored. Lizard optic nerve myelin inhibited extension of rat DRG neurites, and lizard oligodendrocytes elicited DRG growth cone collapse. Both effects were partially reversed by antibody IN-1 against mammalian 35/250 kD neurite growth inhibitors, and IN-1 stained myelinated fiber tracts in the lizard CNS. However, lizard RGC growth cones grew freely across oligodendrocytes from the rat and the reptilian CNS. Mammalian CNS myelin proteins reconstituted into liposomes and added to elongating lizard RGC axons caused at most a transient collapse reaction. Growth cones always recovered within an hour and regrew. Thus, lizard CNS myelin and oligodendrocytes possess nonpermissive substrate properties for DRG neurons--like corresponding structures and cells in the mammalian CNS, including mammalian-like neurite growth inhibitors. Lizard RGC axons, however, appear to be far less sensitive to these inhibitory substrate components and therefore may be able to regenerate through the visual pathway despite the presence of myelin and oligodendrocytes that block growth of DRG neurites.     

Linking service climate and customer perceptions of service quality: test of a causal model

A set of foundation issues that support employee work and service quality is conceptualized as a necessary but not sufficient cause of a climate for service, which in turn is proposed to be reflected in customer experiences. Climate for service rests on the foundation issues, but in addition it requires policies and practices that focus attention directly on service quality. Data were collected at multiple points in time from employees and customers of 134 branches of a bank and analyzed via structural equation modeling. Results indicated that the model in which the foundation issues yielded a climate for service, and climate for service in turn led to customer perceptions of service quality, fit the data well. However, subsequent cross-lagged analyses revealed the presence of a reciprocal effect for climate and customer perceptions. Implications of these results for theory and research are offered.     

Stability of fumonisins in thermally processed corn products

Little is known about the stability of fumonisins in corn-based foods during heating. This study investigated the effects of canning, baking, and roasting (dry heating) processes on the stability of fumonisins in artificially contaminated and naturally contaminated corn-based foods. All samples were analyzed for fumonisin levels by both a commercial enzyme-linked immunosorbent assay (ELISA) and a high-performance liquid chromatographic (HPLC) method. Canned whole-kernel corn showed a significant (P < or = 0.05) decrease in fumonisins by both ELISA (15%) and HPLC (11%) analyses. Canned cream-style corn and baked corn bread showed significant (P < or = 0.05) decreases in fumonisin levels at an average rate of 9% and 48%, respectively, as analyzed by ELISA. Corn-muffin mix artificially contaminated with 5 micrograms of fumonisin B1 (FB1) per g and naturally contaminated corn-muffin mix showed no significant (P < or = 0.05) losses of fumonisins upon baking. Roasting cornmeal samples artificially contaminated with 5 micrograms of FB1 per g and naturally contaminated cornmeal samples at 218 degrees C for 15 min resulted in almost complete loss of fumonisins.     

Effect of propranolol and nifedipine on maximal electroshock-induced seizures in mice: individually and in combination

To clarify the influence of the head-up position on cerebral oxygen metabolism during laparoscopy with CO2 insufflation in 12 patients who underwent laparoscopic cholecystectomy, changes in the concentrations of cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (total Hb) and oxidized cytochrome aa3 (Cyt aa3) were measured by use of near-infrared laser spectroscopy. Anesthesia was maintained with nitrous oxide (66%), oxygen, and sevoflurane. Pneumoperitoneum was maintained at an intraabdominal pressure of 10-12 mm Hg by use of CO2. Minute ventilation was adjusted to maintain end-tidal CO2 tension (P(ET)CO2) between 35 and 40 mm Hg during the procedure. Patients were moved from supine to the head-up (20 degree) position before intraabdominal manipulation. The concentration of HbO2 decreased significantly when patients were moved to the head-up position and 30 min thereafter. It remained significantly low after they were returned to the supine position and at the end of surgery. The concentration of Hb was unchanged during the study. Therefore, the concentration of total Hb decreased significantly when patients were moved to the head-up position, as well as 30 min thereafter. It remained significantly low after they were returned to the supine position and at the end of surgery. The concentration of Cyt aa3, however, did not change significantly during the study. These results suggest that the head-up position during laparoscopic cholecystectomy decreases cerebral HbO2 and total Hb.     

Regulation of Sos activity by intramolecular interactions

The guanine nucleotide exchange factor Sos mediates the coupling of receptor tyrosine kinases to Ras activation. To investigate the mechanisms that control Sos activity, we have analyzed the contribution of various domains to its catalytic activity. Using human Sos1 (hSos1) truncation mutants, we show that Sos proteins lacking either the amino or the carboxyl terminus domain, or both, display a guanine nucleotide exchange activity that is significantly higher compared with that of the full-length protein. These results demonstrate that both the amino and the carboxyl terminus domains of Sos are involved in the negative regulation of its catalytic activity. Furthermore, in vitro Ras binding experiments suggest that the amino and carboxyl terminus domains exert negative allosteric control on the interaction of the Sos catalytic domain with Ras. The guanine nucleotide exchange activity of hSos1 was not augmented by growth factor stimulation, indicating that Sos activity is constitutively maintained in a downregulated state. Deletion of both the amino and the carboxyl terminus domains was sufficient to activate the transforming potential of Sos. These findings suggest a novel negative regulatory role for the amino terminus domain of Sos and indicate a cooperation between the amino and the carboxyl terminus domains in the regulation of Sos activity.