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This study was conducted to ascertain whether there is any advantage to the continuous-infusion femoral 3-in-1 nerve block over the single-injection femoral nerve block for postoperative analgesia after total knee arthroplasty.A double-blind, randomized, controlled study was made of 33 patients undergoing total knee arthroplasty, who were randomized into three groups. Group 1 received a single-injection femoral 3-in-1 nerve block with 20 mL 0.5% bupivacaine with 1:200,000 epinephrine. Group 2 had a catheter placed in the femoral nerve sheath, through which a continuous femoral 3-in-1 nerve block was established. Group 3 patients served as controls. All blocks were performed and assessed prior to induction of standardized general anesthesia. All patients received morphine via patient-controlled analgesia. Pain was recorded on a 100-mm visual analog scale at rest and with motion of the knee. Opioid consumption and side effects were recorded; P = .05 was considered statistically significant.In the recovery room, pain scores with motion were lower in the single-injection and continuous-infusion groups (P.05). There were no significant differences between any of the groups regarding pain scores or morphine requirements beyond the recovery room. The incidence of nausea was higher in the control group. There were no differences between the groups with respect to overall patient satisfaction.We were unable to confirm improvements in analgesia provided by continuous-infusion femoral 3-in-1 nerve block for total knee arthroplasty except in the recovery room.

In order to characterize the dynamics of CGG repeat instability at the fragile X syndrome locus (FMR1 gene), we have used small pool PCR to estimate the mutation rate within germline (sperm) and somatic tissue (leukocytes) of two normal males, one carrying the most common 29 CGG repeats allele, the other carrying a borderline normal-premutated allele of 55 repeats. Large contractions and moderate expansions of the repeat were found in sperm and blood for the 55 repeat allele while almost no variation was found in sperm or blood with the 29 repeat allele. Somatic blood DNA exhibited fewer expansions and contractions than sperm. Contractions were more frequent than expansions, and all the expansions were found in the +4 to +10 repeats range, while most of the contractions were found in the -10 to -30 range, suggesting that a subset of contractions results from a distinct mechanism. These results also suggest that the dynamics of the CGG repeat could be partly due to germline instability within the high normal or premutated ranges.

In a fragile X family referred for prenatal diagnosis, the female fetus did not inherit the full fragile X mutation from her mother, but an unexpected expansion within the normal range of CGG repeats from 29 to 39 was observed in the paternal X chromosome. Also, a rare recombination between DXS548 and FRAXAC1 was recorded in the maternal meiosis. Follow up of the neonate confirmed the same DNA genotype as in the CVS, but the child died of DiGeorge syndrome after four days and was subsequently found to carry a microdeletion of chromosome 22 using probe cEO. It is suggested that in this family the deletion of chromosome 22 is likely to be a chance event but the rare recombinant and the fragile X mutation might be causally related.

Background Localised CAG repeat expansion is a characteristic of both human HD and mouse model brains and could potentially contribute to the development of cellular dysfunction through the expression of progressively longer poly Q containing protein. A derivative of the R6/1 mouse expressing 89Q (Vatsavayai et al (2007) Brain Res. Bull) provides an ideal opportunity to assess expansion in an early, preclinical-like model. Aims To characterise timing, extent and patterns of expression of somatically expanded CAG repeats in neuronal and glial cell populations of the cortico-striatal-nigral pathways, including white matter (corpus callosum), and to assess the extent of localised changes in glial cell populations in relation to phenotype development. Methods PCR analysis of gDNA and mRNA isolated from cortico-striatal-nigral regions was used to provide an index of polyQ loading in cells from 2 to 20 months of age alongside determination of weight loss and motor phenotype onset. Additional glial and neuronal cell markers (transgene, GFAP, TH) were assessed in the first 12 months of age. Results The 89Q phenotype is significantly milder than that seen in R6/1 116Q, with weight loss being a more robust marker of progression than motor deficits (clasping). mRNAs carrying expanded CAG repeats have been identified in neurons in the cortico-striatal-nigral axis by 2 months of age, being more extensive in striatal and substantia nigra neurons, well before any recorded phenotypic or electrophysiological deficits have been observed. Expansion profiles in both gDNA and mRNA indicate that regional and cell-specific differences are present. Expansion is extensive in glial cell populations and in corpus callosum and changes in cell markers suggest glial cell changes, although no evidence for activation is found. Conclusions CAG expansion starts early and continues in all cortical-striatal-nigral neurons, indicating that these cells are exposed to transgenic protein carrying progressively longer polyglutamine tracts. The slow and more progressive development of phenotypic features in the 89Q mouse confirm that this animal presents an ideal opportunity to investigate early events that might represent presymptomatic or early Huntington9s disease.

Background There is growing evidence that the earliest symptoms of Huntington9s disease (HD) are attributable to abnormalities in synaptic and cell function. The advent of predictive gene testing combined with PET imaging has revealed an early loss of dopamine receptors in asymptomatic gene carriers. We have previously shown that cortical synaptic plasticity is abnormal in HD mice and can be rescued by dopaminergic therapy (Cummings et al (2006) Human Molecular Genetics; Dallerac et al (2011) Neurodegen. Dis.). Aim To assess the electrophysiological properties of mid-brain dopaminergic neurons and their ability to release dopamine in 89Q (preclinical; Vatsavayai et al (2007) Brain Res. Bull.) and 116Q (symptomatic) R6/1 mice. Methods Brain slices were prepared from 89Q and 116Q R6/1 mice and controls aged 9–11 months. Intracellular recordings were made from dopaminergic neurons located in the substantia nigra. Evoked release of striatal dopamine was measured using amperometry. Results Resting membrane potentials and input resistances were normal, however 116Q and 89Q tg dopaminergic neurones exhibited a statistically significant decrease in the amplitude and duration of the slow after hyperpolarisation and a marked increase in firing rate upon depolarisation. Evoked dopamine release was dramatically reduced in 116Q slices compared with controls. Unexpectedly, the converse was found for slices prepared from 89Q mice. Maximal dopamine release in these slices was significantly greater than controls. Conclusions These data suggest that (i) dopaminergic neurons are abnormal and (ii) activity-dependent dopamine release undergoes a temporal biphasic shift from a supra level of release to an abnormally low one; a profile that may underlie and contribute to the pathogenic and symptomatic complexity of HD. Collectively, our findings suggest that the dopamine system may represent a site for intervention in the early pathogenesis of HD.

Kaplan-Meier risks estimates are calculated and compared for two consecutive series (N1 = 840, N2 = 819) of first-degree relatives of Alzheimer disease (AD) patients diagnosed as either "probable" or "autopsy-confirmed" AD. The consistency of results increases confidence in estimates and suggests consistent case ascertainment over 8 years. Lifetime risk estimates to age 88 for the combined sample (23.4% +/- 3.0%) do not approach the 50% risk compatible with an autosomal dominant model of transmission. These results support our previous finding and suggest that an autosomal dominant gene(s) is not responsible for all cases of AD.

10025 Background: Sorafenib has a low single agent RR in sarcoma. Other angiogenesis inhibitors are more effective when combined with standard chemotherapy. Sorafenib has been safely combined with dacarbazine for treatment of melanoma. As PRs, MRs and prolonged SD were seen in LMS, SS and MPNST in our single agent S study, we chose to investigate S+D in those histologies. Methods: Patients with LMS, SS or MPNST with up to 2 priors, and adequate hepatic, renal and marrow function receive S at 400 mg BID and D at 1000mg/m2 every 3 weeks. Pts are restaged every 2 cycles. The primary objective of this trial is to determine Clinical Benefit Response rate (CBR=CR+PR + SD x18 weeks) of S+D in these subtypes. A Simon two stage design to distinguish between a CBR rate of 20% and 40% required 4 CBRs out of the first 17 pts to expand to a second cohort, and 11/37 (29.7%) CBRs to be considered positive. Results: From 2/09-12/10, 31 pts have been enrolled: 17 F, 14 M; median age 55, range 27-80; ECOG PS 0 16, 1 14; 20...

FRAXA is unique amongst fragile sites in that it is intimately involved with a specific clinical phenotype, the fragile X syndrome. Whilst the majority of fragile X individuals have been found to have a characteristic mutation in the FMR1 gene, a small proportion of individuals exhibiting fragility have no such mutation. Investigation of the site of chromosome fragility in these FMR1 mutation negative, fragile X site positive individuals, has identified a second site of fragility, FRAXE. However, the presence of FRAXE has not explained all such cases. Here we describe a fragile X site positive, FMR1 mutation negative family, in which chromosome fragility is not due to the FRAXA or FRAXE but is due to a third site designated FRAXF. Using fluorescent in situ hybridisation (FISH) this site is shown to lie over 1Mb distal to FRAXA. The identification of a third fragile site in this small region of the X chromosome provides an opportunity to extend our studies of the molecular nature of chromosome fragility.

A master equation approach to the limiting efficiencies of solar cells with molecular absorbers is presented. A number of model absorbers are analyzed that possess identical absorption spectra, but with differing numbers of electronic excited states. The Shockley–Queisser limit is reproduced for a molecule resembling a semiconductor, with an infinity of electronic levels in the excited state manifold. However, when only a few electronic states contribute to the absorption spectrum, the limiting efficiency is reduced. In the extreme case, where only a single electronic excited state participates in the absorption spectrum, the efficiency limit is 28.9%. At high energy thresholds, built-in thermal up-conversion results in solar cells with efficiencies exceeding the Shockley–Queisser curve. The analysis is applicable to any single threshold photovoltaic device, including those based on semiconductor, polymer, and small molecule absorbers.

An amplification of a highly unstable DNA element has been identified at the fragile X locus in Xq27.3. This sequence appears to be both the source of the primary mutation causing the fragile X syndrome, apparently having its causative effect through the methylation of the FMR-1 HTF island and the region of cytogenetic fragility. The direct analysis of the genotype of carrier and affected individuals can be used as a direct diagnosis tool which will improve both the accuracy and speed of diagnosis. The identification of hereditary unstable DNA in a disease with such a wide level of non-penetrance and variable phenotype may give clues as to the basis of non-penetrance in other human genetic disorders.

In this study, 40 families segregating for fragile X [fra (X)] syndrome were examined for the presence of a mutation within the FMR-1 gene. Using the DNA probe Ox1.9, both carriers and affected individuals were found to contain an insertion/amplification-type of mutation with somatic instability. Variability in the size of the mutation, which ranged from less than 0.2 kb to approximately 13 kb, was observed both between individuals (even from the same family) and within individuals, who showed a smear rather than a discrete band(s) on Southern blot analysis. Transmission of the mutation by males resulted in little change of its size, while transmission by females usually resulted in an increase in size. Correlations were observed between the size of inserted/amplified DNA and the level of chromosome fragility and the presence or absence of mental impairment. Overall, a mutation was detected in 66 of 67 (99%) clinically affected males, in 12 of 13 (92%) transmitting males and in 95 of 112 (85%) carrier females. Equivocal results were obtained in 12 (11%) of the carrier females. No mutation was detected in 58 females and 33 males predicted to be normal by linkage, or in one female and 36 normal control males. These results strongly suggest that the mutation detected by Ox1.9 is closely associated with the cytogenetic and clinical expression of fra (X) syndrome. Additionally, the use of this probe along with other probe/enzyme combinations should provide a sensitive clinical assay for the detection of carriers of fra (X) syndrome.

Carriers of the fragile X mutation possess more than the normal number of copies of a trinucleotide repeat (CGG) within the coding region of a gene designated as FMR-1 in Xq27. The clinical phenotype is determined by the number of copies of the CGG repeat. DNA-based methods for the detection of the fragile X mutation are now available which greatly assist in the genetic diagnosis of this disorder. Direct detection of the mutation enables the identification of fragile X negative normal transmitting males and fragile X negative carrier females.

The molecular analysis of human X-linked disease has progressed rapidly over the last few years owing to advances in power of mapping techniques. Physical DNA maps covering more than 5 million base pairs have been constructed for several chromosomal regions. Many of these regions have now also been cloned into overlapping cosmid and YAC contigs facilitating the search for disease genes. The recent identification of the mutation in the fragile X syndrome is such an example of the power of YAC technology in the characterization of human genetic disease mutations.

We have studied families segregating for the fragile X syndrome for the presence of amplification of the CGG repeat sequence adjacent to the HpaII Tiny Fragment (HTF) island in the FMR-1 gene. We demonstrate that 138/143 fragile X positive, mentally retarded males show a characteristic smear of fragments corresponding to somatic variation in the amplification of the CGG sequence. In 7/8 normal transmitting males (NTM's), we show that there is a small amplification of sequence but no evidence for somatic variation. Defined mutated fragments in the size range found in NTM's are seen in daughters of NTM's. The daughters of these female carriers show either a defined fragment in the NTM size range, a defined larger fragment or a heterogeneous pattern of fragments. In the latter 2 cases the clinical phenotype of the females cannot easily be predicted, presumably because of variable X inactivation. In some families, the observed DNA genotype does not correlate with the phenotype; in others we demonstrate the occurrence of individuals with a mosaic DNA genotype. The implications of these data for diagnosis of the disease are discussed.

The fragile X syndrome is a common cause of mental retardation and is associated with a fragile site at Xq27.3 (FRAXA). Recently, evidence has been presented for the role of methylation and genomic imprinting in the expression of the disease. We have identified a site of methylation in patients by long range restriction mapping of the region. In this paper we present a YAC contig of this area, localise the CpG sequences which are methylated, and show by in situ hybridisation that the site of fragility lies within this region.

We have used recombinant clones derived from microdissection of the fragile X region to characterize breakpoints around the fragile site at Xq27.3. So far, no microdissection markers derived from Xq28 material have been found, thus allowing a rapid screening for clones surrounding the fragile site by their presence in a somatic cell hybrid containing Xq27.2-Xqter. A total of 43 new DNA markers from Xq27 have been sublocalized within this chromosome band. Of these new DNA markers, 5 lie in an interval defined as containing the fragile X region. The saturation of Xq27 with DNA markers by microdissection demonstrates the power of this technique and provides the resources for generating a complete physical map of the region.

Free radicals, induced by ionising radiation or generated by chemical systems, are known to produce DNA damage that may result in mutation. An in vitro study was carried out to discover whether free radicals produced from water using kHz ultrasound increased the mutation rate of Salmonella typhimurium above the spontaneous reversion rate. Results showed that the mutation rate of S. typhimurium did not increase under these conditions. It is concluded that dental ultrasound is not mutagenic to the dental soft tissues under normal conditions of use.

We have localized the gene encoding a cerebellar degeneration related (CDR) protein to a region proximal to the fragile site close to DXS98 and DXS105. This gene is polymorphic with the enzyme RsaI and therefore also provides a new genetic marker in this region. We have refined the localization of the locus DXS304 distal to the breakpoint in a patient suffering from Hunter disease. This confirms the localization of DXS304 distal to the fragile site previously suggested by linkage studies and localizes the fragile X mutation to a relatively small region between the Hunter breakpoint and the breakpoint in another hybrid B17.

We describe the molecular cloning of the rearranged HRAS1 oncogene found in association with the increased tumorigenic potential of the chromosome mediated gene transfectant E65.5. The rearrangement occurs immediately 3' to the c-Ha-ras coding region, removing the variable numbered tandem repeat (VNTR) but not altering the HRAS1 transcription unit. The novel 3' DNA sequence contains a short open reading frame but shows no homology to any previously cloned elements. Sequence analysis identifies a number of short DNA motifs consistent with the activity of an aberrant recombinogenic mechanism.

We have microdissected and cloned the region around the fragile site at Xq27.3 on the human X chromosome. All of the clones tested map to the Xq27-Xq28 region, and detailed mapping on a panel of somatic cell hybrids indicates that the microdissected library contains sequences derived from both sides of the fragile X mutation. Some of these clones give signals in rodent DNA. This library demonstrates the power of microdissection for the identification of potential coding sequences near a disease locus and provides a promising resource for the identification of the fragile X mutation.

The enaminoester 1-benzyl-2-ethoxycarbonylmethyleneimidazolidine reacts with α,β-enones and other Michael acceptors to give 1,4-adducts; removal of the ethoxycarbonyl group completes overall conjugate addition of the imidazoline α-anion (which itself adds 1,2 to enones), and hydrolysis affords carboxylic acids.

Expansion of an unstable (CGG)n repeat to over 200 triplets within the promoter region of the human FMR1 gene leads to extensive local methylation and transcription silencing, resulting in the loss of FMRP protein and the development of the clinical features of fragile X syndrome. The causative link between (CGG)n expansion, methylation and gene silencing is unknown, although gene silencing is associated with extensive changes to local chromatin architecture. In order to determine the direct effects of increased repeat length on gene transcription in a chromatin context, we have examined the influence of FMR1 (CGG)n repeats upon transcription from the HSV thymidine kinase promoter in the Xenopus laevis oocyte. We observe a reduction in mRNA production directly associated with increasing repeat length, with a 90% reduction in mRNA production from arrays over 100 repeats in length. Using a kinetic approach, we show that this transcriptional repression is concomitant with chromatin maturation and, using in vitro transcription, we show that chromatin formation is a fundamental part of the repressive pathway mediated by (CGG)n repeats. Using Trichostatin A, a histone deacetylase inhibitor, we show reactivation of the silenced promoter. Thus, isolated fragile X associated (CGG)n repeat arrays can exert a modifying and transcriptionally repressive influence over adjacent promoters and this repressive phenomenon is, in part, mediated by histone deacetylation.

[1] The transient and long-term adjustment process of the Antarctic Circumpolar Current (ACC) in response to global warming in the CSIRO climate model is examined in an integration, which is run under increasing atmospheric CO2 following the IPCC/IS92a scenario to stabilisation at triple the initial CO2 concentration (3 × CO2). The ACC transport through Drake Passage shows an evident strengthening along with the CO2 increase and, in the subsequent period with stabilised 3 × CO2, it keeps increasing steadily after CO2 tripling for a few centuries until a maximum (151 Sv, 17% larger than the initial state) is reached. The strengthening of the ACC transport results from the warming-induced enhancement of the meridional density gradient in the ocean interior across the ACC: it leads to a speedup of the upper layer zonal flow which outweighs the deceleration in the underlying layer caused by the weakening of the deep overturning off Antarctica.

The C-alkylation of 1-benzyl-2-(ethoxycarbonylmethylene)-2,3,4,5-tetrahydroimidazole with halogeno-and dihalogeno-alkanes is described; subsequent removal of the ethoxycarbonyl group provides a new route to 2-alkyl-4,5-dihydroimidazoles. 1,3-Dihalogenoalkanes afford imidazo[1,2-a] pyridines.

We demonstrate that synthetic receptors with carefully positioned binding groups can modulate the rate of a cycloaddition reaction by selectively binding to different structures on the reaction pathway

Output from a coupled atmosphere–ocean model forced by the IS92a greenhouse gas scenario was used to investigate the feedback between climate change and the oceanic uptake of CO 2 . To improve the climate simulation, we used Gent and co-workers eddy parameterization in the ocean and a prognostic equation for export production from the upper ocean. For the period of 1850 to 2100, the change in the oceanic uptake of CO 2 with climate was separated into 3 feedbacks. (i) Climate change warmed the sea-surface temperature which increased the partial pressure of CO 2 in the surface ocean and reduced the accumulated ocean uptake by 48 Gt C. (ii) Climate change reduced meridional overturning and convective mixing and increased density stratification in high latitudes which slowed the transport of anthropogenic CO 2 into the ocean interior and reduced the cumulative ocean CO 2 uptake by 41 Gt C. (iii) Climate change altered “natural” cycling of carbon in the ocean which increased the cumulative ocean CO 2 uptake by 33 Gt C. The change in natural carbon cycling with climate change was dominated by 2 opposing factors. First, the supply of nutrients to the upper ocean decreased which reduced the export of organic matter (by 15% by year 2100) and produced a net CO 2 flux out of the ocean. However, associated with the reduced nutrient supply was the reduction in the supply of dissolved inorganic carbon to the upper ocean, which produced net CO 2 flux into the ocean. For our model, the latter effect dominated. By the year 2100, the combinations of these 3 climate change feedbacks resulted in a decrease in the cumulative oceanic CO 2 uptake of 56 Gt C or 14% of the 402 Gt C of oceanic CO 2 uptake predicted by a run with no climate change. Our total reduction in oceanic CO 2 uptake with climate change for the 1850 to 2100 period was similar to the 58 Gt C reduction in oceanic CO 2 uptake predicted by Sarmiento and Le Quere. However, our consistency with this previous estimate is misleading. By including the Gent and co-workers eddy parameterization in the ocean, we reduced the positive feedback between climate change and the oceanic uptake of CO 2 from 169 to 89 Gt C (80 Gt C change). This reduction reflects a decrease in both sea surface warming and anthropogenic forcing feedbacks. By using a prognostic parameterization of export production, we reduced the negative feedback response of the natural carbon cycle to climate change from 111 to 33 Gt C (78 Gt C). These 2 large offsetting changes in the ocean response to climate change produced only a net change of 2 Gt C. This resulted in a net reduction in oceanic uptake of 2 Gt C from the previous study. DOI: 10.1034/j.1600-0889.1999.t01-1-00012.x

Protonation of 2,6-diamidopyridine with diaryl phosphates leads to a conformational change in the pyridine from inwardly to outwardly directed amide-NH groups and a resultant self-assembly of the anion and cation into an alternating cocrystal with a novel hydrogen bonding motif.

Interannual variations in the large-scale atmospheric and oceanic fields over the tropical Atlantic are studied in relation to rainfall anomalies on the Angola coast. Departure patterns are constructed by stratification with respect to extremely dry and wet years and by correlation with rainfall in Angola, which is concentrated in March–April. The analysis suggests a causality chain of atmospheric-oceanic anomalies. Variations of westward wind stress on the western equatorial Atlantic constitute an early link in this chain. The annual cycle is characterized by a relaxation of the wind stress from September–November to February–March. Anomalous seasonal relaxation of easterly wind stress over the western equatorial Atlantic remotely forces the sea surface temperature (SST) departures in the eastern South Atlantic, a large relaxation being followed by positive SST departures. Sea surface temperature modulates the rainfall over downstream Angola by controlling the atmospheric moisture and stability....

Free equatorial modes for several simple coupled ocean-atmosphere models are determined. They are found to include unstable and damped modes of large zonal scale and long period. The influence of ocean thermo-dynamics on unstable modal behavior is systematically explored. The Model I ocean features a local thermal equilibrium. In Model II, linearized temperature advection is the sole ocean thermal process. The Model III ocean features both advective and local thermal processes, while that of Model IV features only local thermal processes. The ocean and atmosphere are each represented by linear shallow water equations on the equatorial β-plane, and are linked by traditional couplings. A finite difference method with variable resolution is used to find eigenvalues and eigenvectors of the coupled systems. Key results are checked via a series method. Ocean modes are influenced most strongly by coupling, and are damped or destabilized depending on the configuration of induced atmospheric motion relati...

We review simple instabilities in linear theories of coupled atmosphere-ocean models in both bounded and unbounded ocean basins and describe the mechanisms for instability in these linear theories. We then review nonlinear coupled atmosphere-ocean simulations of the El Nino Southern Oscillation (ENSO) phenomenon and relate the instabilities seen in linear theory to the fully nonlinear ENSO simulations. We present a general discussion of the relation between instability and predictability in the ENSO problem and review some recent work on predictability in coupled models. Finally, we comment on some recent predictions in light of our discussion of predictability.

The behavior of a tropical coupled atmosphere/ocean model is analyzed for a range of different background states and ocean geometries. The model is essentially that of Cane and Zebiak for the tropical Pacific, except only temporally constant background states are considered here. For realistic background states and ocean geometry, the model solutions feature oscillations of period of 3–5 yr. By comparing the full model solution with a linearized version of the model, it is shown that the basic mechanism of the oscillation is contained within linear theory. A simple linear analog model is derived that describes the nature of the interannual variability in the coupled tropical atmosphere–ocean system. The analog model highlights the properties that produce coupled atmosphere–ocean instability in the eastern ocean basin, and the equatorial wave dynamics in the western ocean basin that are responsible for a delayed, negative feedback into this instability growth. The growth rate of the local instabil...

2-(1-Ethoxycarbonyl-4-oxoalkyl)-2-imidazolines add organometallic carbon nucleophiles to produce new lactones, whereas hydrogenation affords 1,4,5,6-tetrahydropyridines and piperidines via a novel reductive cyclisation-cleavage pathway.

Although the prevention of false markets is one of the major concerns of stock market authorities in the UK and elsewhere, until recently, the theoretical literature on the workings of markets with imperfect information has been sparse. This paper analyses the problem of providing liquidity to investors when price-sensitive information is unequally distributed. Specifically we shall model the activities of a market-maker when certain traders have price-sensitive information unavailable to other market participants. Our model will show how the bid-asked spread would be determined in such a market. It is useful in explaining certain tactics employed by stock market traders and in suggesting alternative ways of evaluating market efficiency. The theory is developed in three sections: (1) the determination of the bid-asked spread for a single, isolated transaction; (2) the determination of the bid-asked spread in a continuous market; (3) the relationship between the spread and the size of transaction.

The enaminoester 1-benzyl-2-ethoxycarbonylmethyleneimidazolidine reacts with α,β-enones and other Michael acceptors to give 1,4-adducts; removal of the ethoxycarbonyl group completes overall conjugate addition of the imidazoline α-anion (which itself adds 1,2 to enones), and hydrolysis affords carboxylic acids.