Induced electrodeposition of tungsten with nickel from acidic citrate electrolyte

Induced electrodeposition of Ni–W alloys was carried out onto steel substrates from acidic citrate baths (pH 4.5) under different conditions of concentration of electrolyte, current density and temperature. Bright and highly adherent Ni–W deposits were successfully obtained with a relatively high cathodic current efficiency CCE (80–85%). The CCE increases greatly with increasing pH and Ni²⁺ ion content in the bath. The W% in the alloy deposits is in the range of 4–20 wt% depending on the operating condition. The W content in the deposit was found to increase with an increase in Ni²⁺ ion content, pH and temperature. The surface morphology was examined by scanning electron microscopy while the structure of the alloy was examined by X-ray diffraction analysis.     

Using reconfiguration for efficient management of replicated data

Replicated data management protocols have been proposed that exploit a logically structured set of copies. These protocols have the advantage that they provide limited fault-tolerance at low communication cost. The proposed protocols can be viewed as analogues of the read-one write-all protocol in the context of logical structures. In this paper, we start by generalizing these protocols in two ways for logical structures. First, the quorum-based approach is applied to develop protocols that use structured read and write quorums, thus attaining a high degree of data availability for both read and write operations. Next, the reconfiguration or views approach is developed for these structures, resulting in protocols that attain high degrees of availability at significantly low communication cost for read operations. In this sense, the proposed protocols have the advantages of the read-one write-all protocol for low-cost read operations as well as the majority quorum protocol for high data availability. Finally, we generalize the reconfiguration approach to allow for the dynamic reconfiguration of the database system from one replica management protocol to another. This allows database systems to adapt to an evolving and dynamic application environment     

Congenital nephrotic syndrome: a novel phenotype of type I carbohydrate-deficient glycoprotein syndrome

Type I carbohydrate-deficient glycoprotein (CDG) syndrome is a genetic multisystem disorder generally without overt renal problems. We report a neonate with neurological abnormalities and congenital nephrotic syndrome of diffuse mesangial sclerosis type. Serum transferrin isoelectric focusing showed the typical abnormalities of type I CDG syndrome. Normal transferrin focusing findings in other patients with similar renal problems excluded the possibility of a secondary biochemical phenomenon. The diagnosis of type I CDG syndrome was confirmed by demonstration of a deficiency of phosphomannomutase. No evidence of pontocerebellar atrophy was found in imaging or at autopsy. We conclude that congenital nephrotic syndrome may occur in type I CDG syndrome, and that this diagnosis should be considered in patients with congenital nephrotic syndrome. Absence of pontocerebellar atrophy does not exclude the diagnosis of type I CDG syndrome.     

Oxidant--nitric oxide signalling mechanisms in vascular tissue

Nitric oxide has several signalling mechanisms that can potentially control force generation by vascular smooth muscle. Some of these mechanisms include the stimulation of cGMP production by the soluble heme-containing form of guanylate cyclase (sGC), inhibition of mitochondrial respiration, and the modulation of vasoactive mediator release by the endothelium. Reactive O2 species (ROS) can also regulate force generation by vascular smooth muscle through mechanisms including the stimulation of production of vasoactive prostaglandins, the stimulation of sGC by catalase-mediated metabolism of H2O2 and inhibition of sGC activation by superoxide, the activation of protein kinase C, and the modulation of mediator release from the endothelium. Interactions between NO and ROS signalling mechanisms result in additional processes which modulate vascular force generation. For example, NO-elicited stimulation of sGC can be attenuated by superoxide, and this results in the formation of peroxynitrite (ONOO-). However, high levels of NO result in a ONOO- and thiol dependent formation of a species which regenerates NO in a time-dependent manner. It appears that NO inhibits catalase through an O2 and superoxide dependent process which results in inhibition of relaxation mediated by H2O2-elicited stimulation of sGC. Furthermore, evidence exists suggesting additional signalling mechanisms resulting from interactions between regulatory systems involving NO and ROS which appear to be important in control of vascular force generation in pathophysiological states.     

Cardiovascular and metabolic costs of forward, backward, and lateral motion

PURPOSE: The purpose of this study was to compare the metabolic and cardiovascular responses of movement in forward (FM), backward (BM), and lateral (LM) directions. METHODS: Thirteen athletes with the following characteristics (mean +/- SD) were evaluated: age 21+/-3 yr, height 172.0+/-9.0 cm, weight 62.92+/-9.05 kg, and VO2max 54.13+/-7.42 mL x kg(-1) x min(-1). Subjects were evaluated at 80.45 and 134.08 m x min(-1). A repeated measures ANOVA was used for statistical analysis (P < 0.05). RESULTS: At 80.45 m x min(-1), the following respective VO2 mL x kg(-1) x min(-1) and heart rate (HR) beats x min(-1) responses were: FM = 12.42+/-2.29, 113+/-10; BM = 15.95+/-2.45, 132+/-16; and LM = 22.10+/-4.76, 140+/-15. Both VO2 and HR were significantly different between conditions: LM > BM > FM. At 134.08 m x min(-1), the following respective VO2 and HR responses were: FM = 27.15+/-2.51, 146+/-7; BM = 31.33+/-5.77, 168+/-11; and LM = 32.58+/-5.74, 169+/-10. At 134.08 m x min(-1) neither HR or VO2 were significantly different between LM or BM (LM, BM, > FM). Stride length and stride frequency were also significantly different between conditions. These results indicate the variation in the energy cost of FM, BM, and LM.     

I-SceI-induced gene replacement at a natural locus in embryonic stem cells

Gene targeting is a very powerful tool for studying mammalian development and physiology and for creating models of human diseases. In many instances, however, it is desirable to study different modifications of a target gene, but this is limited by the generally low frequency of homologous recombination in mammalian cells. We have developed a novel gene-targeting strategy in mouse embryonic stem cells that is based on the induction of endogenous gap repair processes at a defined location within the genome by induction of a double-strand break (DSB) in the gene to be mutated. This strategy was used to knock in an NH2-ezrin mutant in the villin gene, which encodes an actin-binding protein expressed in the brush border of the intestine and the kidney. To induce the DSB, an I-SceI yeast meganuclease restriction site was first introduced by gene targeting to the villin gene, followed by transient expression of I-SceI. The repair of the ensuing DSB was achieved with high efficiency (6 x 10[-6]) by a repair shuttle vector sharing only a 2.8-kb region of homology with the villin gene and no negative selection marker. Compared to conventional gene-targeting experiments at the villin locus, this represents a 100-fold stimulation of gene-targeting frequency, notwithstanding a much lower length of homology. This strategy will be very helpful in facilitating the targeted introduction of several types of mutations within a gene of interest.     

Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with body mass index

AIMS: To investigate the relationship in patients with heart failure between BP response to the first dose of ACE inhibitor and (1) plasma drug concentration and (2) baseline clinical and laboratory variables. METHODS: We studied individual placebo-corrected BP responses to initiation of treatment with one of a number ACE inhibitor preparations in 132 patients with mild to moderate CHF. Various pharmacokinetic/pharmacodynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP response as assessed directly from the AUC(0,10 h) and indirectly from the slope of the PK/PD relationship. Predictive models for response variables were developing using regression analysis. RESULTS: BP response was primarily related to plasma drug concentration. The association between the fall in BP and baseline variables was weak. The strongest single predictor of BP response was baseline mean arterial pressure (r2 = 5.8%, P = 0.02). The best combinations of predictor variables contained mean arterial pressure, plasma renin activity, creatinine concentration and age (r2 = 14.4%, P = 0.37). When the choice of ACE inhibitor was added, the predictive power of the model increased (r = 23.6%, P < 0.01) but left the majority of the variability in response unexplained. CONCLUSIONS: The first-dose blood pressure response to ACE inhibition cannot be accurately predicted from baseline pathophysiological variables in patients with mild to moderate CHF. The choice of ACE inhibitor accounts for a small proportion of the variability in response but wide inter-individual variability exists in the response to each treatment.     

An ester bond linking a fragment of a serine proteinase to its serpin inhibitor

Most known members of the serpin superfamily are serine proteinase inhibitors. Serpins are therefore important regulators of blood coagulation, complement activation, fibrinolysis, and turnover of extracellular matrix. Serpins form SDS-resistant complexes of 1:1 stoichiometry with their target proteinases by reaction of their P1-P1' peptide bond with the active site of the proteinases. The nature of the interactions responsible for the high stability of the complexes is a controversial issue. We subjected the complex between the serine proteinase urokinase-type plasminogen activator (uPA) and the serpin plasminogen activator inhibitor-1 (PAI-1) to proteolytic digestion under nondenaturing conditions. The complex could be degraded to a fragment containing two disulfide-linked peptides from uPA, one of which included the active site Ser, while PAI-1 was left undegraded. By further proteolytic digestion after denaturation and reduction, it was also possible to degrade the PAI-1 moiety, and we isolated a fragment containing 10 amino acids from uPA, encompassing the active site Ser, and 6 amino acids from PAI-1, including the P1 Arg. Characterization of the fragment gave results fully in agreement with the hypothesis that it contained an ester bond between the hydroxyl group of the active site Ser and the carboxyl group of the P1 Arg. These data for the first time provide direct evidence that serine proteinases are entrapped at an acyl intermediate stage in serine proteinase-serpin complexes.     

Selective disruption by protein kinases of G-protein-mediated Ca2+ channel modulation

1. We studied the effects of phorbol-12-myristate, 13-acetate (PMA) on G-protein-mediated inhibition of Ca2+ channels by several neurotransmitters in rat superior cervical ganglion (SCG) sympathetic neurons, with the use of the whole cell patch clamp. PMA attenuated membrane-delimited inhibition of calcium currents (ICa) by norepinephrine (NE) and somatostatin by more than half, but did not attenuate inhibition by M1 muscarinic receptors, which use a diffusible cytoplasmic messenger. Inhibition of ICa by NE through pertussis-toxin-sensitive and -insensitive G proteins was equally attenuated by PMA. PMA enhanced ICa in about half the neurons (enhancement of 10 +/- 1%, mean +/- SE) and strongly reduced the holding current in 44 of 61 cells. 2. The M-type K+ current (IM) was not suppressed by PMA, and PMA did not attenuate inhibition of IM by muscarinic agonists, which is also via a diffusible cytoplasmic messenger. 3. Attenuation of NE and somatostatin inhibition by PMA was blocked by 1 microM staurosporine, a broad-spectrum protein kinase inhibitor. Tests with three inhibitors selective for distinct isoforms of protein kinase C (PKC) gave mixed results. PMA's actions were unaffected by 1 microM calphostin C, blocked by 500 nM bisindolylmaleimide, and unaffected by the pseudosubstrate inhibitor PKC19-36. 4. Thus we find that two membrane-delimited signaling pathways that inhibit ion channels in rat SCG neurons are strongly attenuated by PMA, but signaling pathway(s) that use a diffusible cytoplasmic messenger are not. We speculate that a nonstandard PKC isoform, perhaps PKC mu, mediates PMA actions.