bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of the absorption of concentrated dyes and their use for quantitative imaging of surface topography
Authors: MODEL M. A. , KHITRIN A. K. , BLANK J. L.
Published: July 2008

We propose a method to image the surface topography of transparent objects. The space between the object and the opposite closely positioned surface (such as a cover glass or a slide) is filled with a strongly absorbing dye. The contrast is generated by recording a transmission image at a wavelength where the dye absorbs. Since the transmitted intensity depends on the depth of the dye layer, it carries information about the relief of the tested surface. With sufficiently concentrated dyes, nanometre unevenness of a surface can be detected. By using less‐concentrated solutions, it is possible to image and measure larger objects, such as biological cells. At the present stage, biological applications of the method are only semi‐quantitative, but the method still provides detailed information about cell shapes that is not readily obtainable with other imaging techniques.

 Conversion of the image grey scale into the units of vertical distance requires knowledge of the absorption coefficient of the dye. The same method that is used for imaging can be adapted to measure the absorption coefficient of concentrated dyes. The solution to be analyzed is placed between a glass slide and a spherical lens of known radius. The absorption coefficient is determined from attenuation of transmitted intensity as a function of the distance to the centre. At the same time, the interference pattern in the reflected image allows measurement of the refractive index of the dye.
Climbing the steps of viral atomic force microscopy: visualization of Dengue virus particles
Authors: FERREIRA G. P. , TRINDADE G. S. , VILELA J. M. C. , DA SILVA M. I. N. , ANDRADE M. S. , KROON E. G.
Published: July 2008

In recent years, the application of atomic force microscopy (AFM) to biological systems has highlighted the potential of this technology. AFM provides insights into studies of biological structures and interactions and can also identify and characterize a large panel of pathogens, including viruses. The Flaviviridae family contains a number of viruses that are important human and animal pathogens. Among them, Dengue virus causes epidemics with fatal outcomes mainly in the tropics. In this study, Dengue virus is visualized for the first time using the in air AFM technique. Images were obtained from a potassium‐tartrate gradient‐purified virus. This study enhances the application of AFM as a novel tool for the visualization and characterization of virus particles. Because flavivirus members are closely related, studies of the morphologic structure of the Dengue virus can reveal strategies that may be useful to identify and study other important viruses in the family, including the West Nile virus.
A simple technique to minimize heat damage to specimens during thermal polymerization of LR White in plastic and gelatin capsules
Authors: BOWLING A. J. , VAUGHN K. C.
Published: July 2008

London Resin (LR) White is a commonly used resin for embedding specimens to be used for immuno‐ and/or cytochemical studies. In some instances, due to either the properties of the specimen or the availability of various reagents and equipment, it becomes necessary and/or more convenient to polymerize LR White using heat rather than chemical accelerators or UV light. It is known, however, that heat can reduce or even eliminate the anti genicity of the tissue being embedded. It is therefore desirable to polymerize specimens at the lowest temperature possible and to remove the specimens from the oven as soon as polymerization is complete. We have developed a technique that provides a visual marker that allows the exothermic polymerization of LR White to be monitored, thus minimizing the amount of time a specimen must stay in the oven while excluding oxygen from capsules of polymerizing LR White.
Differential gene expression during thermal stress and bleaching in the Caribbean coral Montastraea faveolata
Authors: DESALVO M. K. , VOOLSTRA C. R. , SUNAGAWA S. , SCHWARZ J. A. , STILLMAN J. H. , COFFROTH M. A. , SZMANT A. M. , MEDINA M.
Published: July 2008

The declining health of coral reefs worldwide is likely to intensify in response to continued anthropogenic disturbance from coastal development, pollution, and climate change. In response to these stresses, reef‐building corals may exhibit bleaching, which marks the breakdown in symbiosis between coral and zooxanthellae. Mass coral bleaching due to elevated water temperature can devastate coral reefs on a large geographical scale. In order to understand the molecular and cellular basis of bleaching in corals, we have measured gene expression changes associated with thermal stress and bleaching using a complementary DNA microarray containing 1310 genes of the Caribbean coral Montastraea faveolata. In a first experiment, we identified differentially expressed genes by comparing experimentally bleached M. faveolata fragments to control non‐heat‐stressed fragments. In a second experiment, we identified differentially expressed genes during a time course experiment with four time points across 9 days. Results suggest that thermal stress and bleaching in M. faveolata affect the following processes: oxidative stress, Ca2+ homeostasis, cytoskeletal organization, cell death, calcification, metabolism, protein synthesis, heat shock protein activity, and transposon activity. These results represent the first medium‐scale transcriptomic study focused on revealing the cellular foundation of thermal stress‐induced coral bleaching. We postulate that oxidative stress in thermal‐stressed corals causes a disruption of Ca2+ homeostasis, which in turn leads to cytoskeletal and cell adhesion changes, decreased calcification, and the initiation of cell death via apoptosis and necrosis.
Specific residues in the N‐terminal domain of FimH stimulate type 1 fimbriae assembly in Escherichia coli following the initial binding of the adhesin to FimD usher
Authors: Munera Diana , Palomino Carmen , Fernández Luis Ángel
Published: July 2008

Type 1 fimbriae are assembled by the chaperone–usher pathway where periplasmic protein complexes formed between fimbrial subunits and the FimC chaperone are recruited by the outer membrane protein FimD (the usher) for their ordered polymerization and export. FimH adhesin initiates and stimulates type 1 fimbriae polymerization by interacting with FimD. Previously we showed that the N‐terminal lectin domain of FimH (N‐FimH) is necessary for binding of the adhesin to FimD. In this work, we have selected mutants in N‐FimH that reduce the levels of adhesin and type 1 fimbriae displayed in Escherichia coli without altering the levels of FimH in the periplasm. The selected mutations are mostly concentrated in residues G15, N46 and D47. In contrast to other mutations isolated that simply affect binding of FimH to FimD (e.g. C3Y), these variants associate to FimD and alter its susceptibility to trypsin digestion similarly to wild‐type FimH. Importantly, their mutant phenotype is rescued when FimD is activated in vivo by the coexpression of wild‐type FimH. Altogether, these data indicate that residues G15, N46 and D47 play an important role following initial binding of FimH to FimD for efficient type 1 fimbriae polymerization by this outer membrane usher.
Halite cementation and carbonate diagenesis of intra‐salt reservoirs from the Late Neoproterozoic to Early Cambrian Ara Group (South Oman Salt Basin)
Authors: SCHOENHERR JOHANNES , REUNING LARS , KUKLA PETER A. , LITTKE RALF , URAI JANOS L. , SIEMANN MICHAEL , RAWAHI ZUWENA
Published: July 2008

Late Neoproterozoic to Early Cambrian carbonates of the Ara Group form important intra‐salt ‘stringer’ reservoirs in the South Oman Salt Basin. Differential loading of thick continental clastics above the six carbonate to evaporite cycles of the Ara Group led to the formation of salt diapirs, encasing a predominantly self‐charging hydrocarbon system within partly highly overpressured carbonate bodies (‘stringers’). These carbonates underwent a complex diagenetic evolution, with one stage of halite cementation in a shallow (early) and another in a deep (late) burial environment. Early and late halite cements are defined by their microstructural relationship with solid bitumen. The early phase of halite cementation is post‐dated by solid reservoir bitumen. This phase is most pervasive towards the top of carbonate stringers, where it plugs nearly all available porosity in facies with initially favourable poroperm characteristics. Bromine geochemistry revealed significantly higher bromine contents (up to 280 p.p.m.) in the early halite compared with the late halite (173 p.p.m.). The distribution patterns and the (high) bromine contents of early halite are consistent with precipitation caused by seepage reflux of highly saturated brines during deposition of the overlying rock salt interval. Later in burial history, relatively small quantities of early halite were dissolved locally and re‐precipitated as indicated by inclusions of streaky solid bitumen within the late halite cements. Late halite cement also seals fractures which show evidence for repeated reopening. Initially, these fractures formed during a period of hydrothermal activity and were later reopened by a crack‐seal mechanism caused by high fluid overpressures. Porosity plugging by early halite cements affects the poroperm characteristics of the Ara carbonates much more than the volumetrically less important late halite cement. The formation mechanisms and distribution patterns of halite cementation processes in the South Oman Salt Basin can be generalized to other petroliferous evaporite basins.
Peroxisomal Δ3,Δ2‐enoyl CoA isomerases and evolution of cytosolic paralogues in embryophytes
Authors: Goepfert Simon , Vidoudez Charles , Tellgren‐Roth Christian , Delessert Syndie , Hiltunen J. Kalervo , Poirier Yves
Published: July 2008

Δ3,Δ2‐enoyl CoA isomerase (ECI) is an enzyme that participates in the degradation of unsaturated fatty acids through the β‐oxidation cycle. Three genes encoding Δ3,Δ2‐enoyl CoA isomerases and named AtECI1, AtECI2 and AtECI3 have been identified in Arabidopsis thaliana. When expressed heterologously in Saccharomyces cerevisiae, all three ECI proteins were targeted to the peroxisomes and enabled the yeast Δeci1 mutant to degrade 10Z‐heptadecenoic acid, demonstrating Δ3,Δ2‐enoyl CoA isomerase activity in vivo. Fusion proteins between yellow fluorescent protein and AtECI1 or AtECI2 were targeted to the peroxisomes in onion epidermal cells and Arabidopsis root cells, but a similar fusion protein with AtECI3 remained in the cytosol for both tissues. AtECI3 targeting to peroxisomes in S. cerevisiae was dependent on yeast PEX5, while expression of Arabidopsis PEX5 in yeast failed to target AtECI3 to peroxisomes. AtECI2 and AtECI3 are tandem duplicated genes and show a high level of amino acid conservation, except at the C‐terminus; AtECI2 ends with the well conserved peroxisome targeting signal 1 (PTS1) terminal tripeptide PKL, while AtECI3 possesses a divergent HNL terminal tripeptide. Evolutionary analysis of ECI genes in plants revealed several independent duplication events, with duplications occurring in rice and Medicago truncatula, generating homologues with divergent C‐termini and no recognizable PTS1. All plant ECI genes analyzed, including AtECI3, are under negative purifying selection, implying functionality of the cytosolic AtECI3. Analysis of the mammalian and fungal genomes failed to identify cytosolic variants of the Δ3,Δ2‐enoyl CoA isomerase, indicating that evolution of cytosolic Δ3,Δ2‐enoyl CoA isomerases is restricted to the plant kingdom.
Aseptic meningitis and abducens nerve palsy as a serious side effect of high dose intravenous immunoglobulin used in a patient with renal transplantation
Authors: Wright S.E. , Shaikh Z.H.A. , Castillo‐Lugo J.A. , Tanriover B.
Published: July 2008

Abstract: Immune globulin intravenous (human) (IGIV) is effective in the treatment of various autoimmune and inflammatory disorders. Recently, high‐dose IGIV 2 g/kg has been utilized in the treatment of antibody‐mediated rejection in solid organ transplantation. We report a renal transplant recipient who developed aseptic meningitis and diplopia from abducens nerve (cranial nerve VI) palsy following IGIV administration for antibody‐mediated rejection. Potential mechanisms of the IGIV‐related aseptic meningitis are elaborated. Clinicians should be aware of aseptic meningitis and cranial nerve palsy as an adverse reaction to IGIV exposure and monitor for its signs and symptoms.
Physiological Role of Exogenously Applied Glycinebetaine to Improve Drought Tolerance in Fine Grain Aromatic Rice (Oryza sativa L.)
Authors: Farooq M. , Basra S. M. A. , Wahid A. , Cheema Z. A. , Cheema M. A. , Khaliq A.
Published: July 2008

Rice performance under drought stress is mainly impeded by oxidative damage and hampered plant water status, which may be improved by exogenous use of osmoprotectants. In this study, the role of glycinebetaine (GB) to improve drought tolerance in rice (Oryza sativa L.) cultivar Super‐basmati was evaluated. GB was used both as seed and foliar application. For priming, seeds were soaked in 50, 100 and 150 mg l−1 aerated solution of GB for 48 h. At four‐leaf stage, one set of plants was subjected to drought stress, while the other set kept at full field capacity. Drought was maintained at 50 % of field capacity by watering when needed. For exogenous application, 50, 100 and 150 mg l−1 GB levels were applied at five‐leaf stage. Drought stress greatly reduced the rice growth while GB application improved it both under well‐watered and drought conditions. Drought tolerance in rice was strongly related to the maintenance of tissue water potential and antioxidant system, which improved the integrity of cellular membranes and enabled the plant to maintain high photosynthesis. Foliar treatments were more effective than the seed treatments, while among the GB treatment, foliar application with 100 mg l−1 was the most effective.
Breakpoints for posaconazole susceptibility testing: background and discussion about the need of establishing values
Authors: Fleck R. , Hof H.
Published: July 2008

Posaconazole is a new antifungal agent, which exhibits a broad spectrum of activity against fungi including Aspergillus terreus, some zygomycetes and dematiaceous fungi. Out of the group of triazole antifungal agents, it is the only compound for which interpretive breakpoints have not been established have not yet been established for Candida spp. As reliable breakpoints are useful in the practical management of patients with fungal infections, it is desirable to establish the same for all available substances. However, the underlying data of the existing breakpoints for other antifungal agents are of varying quality because of limited clinical data available. Furthermore, these breakpoints are not equally suitable for all testing methods available and they may not be suitable for all species to be tested. From the practical point of view, it is therefore important not only to establish breakpoints for the reference method but also for the inexpensive and easy to perform testing methods, which are suitable for smaller laboratories.
Learning‐associated regulation of polysialylated neural cell adhesion molecule expression in the rat prefrontal cortex is region‐, cell type‐ and paradigm‐specific
Authors: Ter Horst Judith P. F. , Loscher Jennifer S. , Pickering Mark , Regan Ciaran M. , Murphy Keith J.
Published: July 2008

The prefrontal cortex (PFC) is an interconnected set of cortical areas that function in the synthesis of a diverse range of information and production of complex behaviour. It is now clear that these frontal structures, through bidirectional excitatory communication with the hippocampal formation, also play a substantial role in long‐term memory consolidation. In the hippocampus, morphological synaptic plasticity, supported by regulation of neural cell adhesion molecule (NCAM) polysialylation status, is crucial to information storage. The recent description of polysialylated neurons in the various fields of the medial PFC suggests these structures to possess a similar capacity for synaptic plasticity. Here, using double‐labelling immunohistochemistry with glutamic acid decarboxylase 67, we report that the nature of NCAM polysialic acid‐positive neurons in the PFC is region‐specific, with a high proportion (30–50%) of a γ‐aminobutyric acid (GABA)ergic phenotype in the more ventral infralimbic, orbitofrontal and insular cortices compared with just 10% in the dorsal structures of the cingulate, prelimbic and frontal cortices. Moreover, spatial learning was accompanied by activations in polysialylation expression in ventral PFC structures, while avoidance conditioning involved downregulation of this plasticity marker that was restricted to the dorsomedial PFC – the cingulate and prelimbic cortices. Thus, in contrast to other structures integrated functionally with the hippocampus, memory‐associated plasticity mobilized in the PFC is region‐, cell type‐ and task‐specific.
Pre‐ and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment: a study of GIRK‐knockout mice
Authors: Torrecilla Maria , Quillinan Nidia , Williams John T. , Wickman Kevin
Published: July 2008

While the acute inhibitory effect of opioids on locus coeruleus (LC) neurons is mediated primarily by the activation of G protein‐gated inwardly‐rectifying K+(GIRK) channels, the 3′‐5′‐cyclic adenosine monophosphate (cAMP) system has been implicated in the effects of chronic morphine exposure. Presently, the impact of chronic morphine treatment on GIRK‐dependent and GIRK‐independent mechanisms underlying the opioid‐induced inhibition of LC neurons is unclear. Here, opioid‐induced postsynaptic inhibition was studied in LC neurons from wild‐type and GIRK2/GIRK3−/−mice at baseline and following chronic morphine treatment. The postsynaptic inhibition of LC neurons caused by the opioid agonist [Met]5enkephalin (ME) was unaffected by chronic morphine treatment in mice of either genotype. Furthermore, chronic morphine treatment had no effect on the forskolin augmentation of the ME‐induced current in wild‐type LC neurons and only a minor effect on the ME‐induced current in LC neurons from GIRK2/GIRK3−/−mice. Chronic morphine treatment did, however, lead to an increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the LC. Interestingly, while forskolin augmented the EPSC frequency similarly in untreated and morphine‐treated wild‐type mice, as well as untreated GIRK2/GIRK3−/−mice, it failed to increase the frequency of EPSCs in morphine‐treated GIRK2/GIRK3−/−mice. Altogether, the findings suggest that chronic morphine treatment exerts little impact on ion channels and signaling pathways that mediate the postsynaptic inhibitory effects of opioids but does enhance excitatory neurotransmission in the mouse LC.
Nitric oxide dependence of glutamate‐mediated modulation at a vertebrate neuromuscular junction
Authors: Pinard Audrée , Robitaille Richard
Published: July 2008

Recent evidence has revealed a contribution of glutamate in the stereotyped cholinergic neuromuscular transmission. Indeed, receptors, transporters and glutamate itself are present at the neuromuscular junction (NMJ) while glutamate activation of metabotropic receptors (mGluRs) decreases synaptic transmission and mediates depression through presynaptic mechanisms. However, we have shown that the mGluRs are located postsynaptically, inconsistent with the presynaptic action of glutamate. In the present study, we tested whether nitric oxide (NO) serves as a retrograde messenger mediating the distant effect of glutamate. Glutamate or an mGluR agonist [trans‐(1S,3R)‐aminocyclopentanedicarboxylic acid (ACPD)] failed to reduce synaptic transmission in the presence of an NOS inhibitor (3Br7NINa, 3‐bromo‐7‐nitroindazole sodium salt). Moreover, application of 3Br7NINa precluded the effect of the mGluR antagonist MCPG [(S)‐alpha‐methyl‐4‐carboxyphenylglycine] on high‐frequency‐induced synaptic depression. Iontophoretic injections of BAPTA [1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′‐tetraacetic acid] in muscle fibres abolished the effect of trans‐ACPD on synaptic transmission and blocked the mGluR component of depression, indicating the involvement of muscular calcium in mGluR‐induced depression. Also, the use of this protocol unveiled a muscular calcium‐dependent potentiating pathway dependent on cyclo‐oxygenase activity. In addition, local application of trans‐ACPD induced an increase in NO production by muscle fibres visualized with the indicator DAF‐FM (4‐amino‐5‐methylamino‐2′,7′‐difluorofluorescein). This was prevented by 3Br7NINa or the iontophoretic injection of BAPTA. Moreover, motor nerve stimulation (50 Hz, 30 s) induced an increase in DAF‐FM fluorescence that was abolished by 3Br7NINa and MCPG. Hence, the data suggest that the production of the retrograde molecule NO depends on the postsynaptic calcium‐dependent activation of nitric oxide synthase following mGluRs stimulation and is essential for the glutamatergic modulation of synaptic efficacy and plasticity at the NMJ.
Broad neuroprotective profile of nicotinamide in different mouse models of MPTP‐induced parkinsonism
Authors: Anderson D. W. , Bradbury K. A. , Schneider J. S.
Published: July 2008

The factors contributing to substantia nigra pars compacta (SNc) dopamine (DA) neuron death and striatal DA depletion in Parkinson’s disease (PD) are still poorly understood. However, mitochondrial dysfunction, cellular energy depletion and oxidative stress appear to play important roles in the pathogenesis of PD. In view of this, the current study examined the potential of nicotinamide, a form of the B‐complex vitamin niacin, to protect against 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced SNc cell loss and striatal DA depletion in two mouse MPTP models that respond differently to putative neuroprotective agents. Adult male C57Bl/6 mice received nicotinamide (125, 250 or 500 mg/kg i.p.) prior to either acute (four injections in 1 day at 2‐h intervals) or sub‐acute (two injections per day at 4‐h intervals for 5 days) MPTP administration. Striatal DA levels, changes in numbers of tyrosine hydroxylase (TH)‐ and cresyl violet‐stained cells in the SNc at 2 and 6 weeks following the last MPTP exposure were analyzed. Nicotinamide administration resulted in a dose‐dependent sparing of striatal DA levels and SNc neurons in acute MPTP‐treated animals. Only the highest dose of nicotinamide had similar effects in sub‐acute MPTP‐treated animals. At 6 weeks after MPTP exposure, there was some spontaneous recovery of striatal DA levels in both models: neuroprotective effects were still apparent in acute but not sub‐acute MPTP‐treated animals. These results show neuroprotective effects of nicotinamide in different mouse Parkinson models associated with different forms of cell death and suggest that nicotinamide may have broad neuroprotective potential in PD.
Huntingtin interacting protein 1 can regulate neurogenesis in Drosophila
Authors: Moores Justin N. , Roy Sophie , Nicholson Donald W. , Staveley Brian E.
Published: July 2008

Huntington’s disease (HD) is associated with a range of cellular consequences including selective neuronal death and decreased levels of neurogenesis. Ultimately, these altered processes are dependent upon proteins that interact with Huntingtin (Htt) such as the Huntingtin‐interacting protein 1 (Hip1) which has a reduced binding preference to expanded Htt. These effects are similar to those observed with modified Notch signal transduction. As Hip1 plays a key role in endocytosis and intracellular transport, and activation of the Notch signal requires both, we investigated putative links between Hip1 and Notch signaling in flies. We have identified two forms of Hip1 that may be produced through the use of alternative first exons: a version of Hip1 with a lipid‐binding ANTH domain and Hip1ΔANTH lacking this domain. The directed expression of Hip1 decreases, while expression of Hip1ΔANTH increases, the density of sensory microchaetae on the dorsal notum, a classical model of neurogenesis. A reduction in microchaetae density associated with NotchMicrochaetae Deficient (MCD) (NMCD ) alleles is sensitive to both Hip1 and Hip1ΔANTH levels, as are the bristle phenotypes generated by misexpression of deltex, a key mediator of Notch signaling. Genetic studies further demonstrate that the observed effects of Hip1 and of Hip1ΔANTH are sensitive to achaete gene dosage while insensitive to the levels of E(Spl), suggesting a non‐canonical Notch neurogenic signal through a deltex‐dependent pathway. The novel role we describe for Hip1 in Notch‐mediated neurogenesis provides a functional link between Notch signaling and proteins related to HD.
Cue usage in financial statement fraud risk assessments: effects of technical knowledge and decision aid use
Authors: Seow Jean‐Lin
Published: July 2008

This paper investigates the effects of technical knowledge and decision aid use on financial statement fraud risk assessments made by directors and students. More extreme fraud risk assessments are made when participants identify and process larger (smaller) numbers of diagnostic (non‐diagnostic) factors, with technical knowledge driving diagnostic factor identification. Significant decision aid‐technical knowledge effects are also found; decision aid use has a detrimental effect on high‐knowledge directors while improving performance in inexperienced, low‐knowledge students. These results suggest that although decision aids can afford gains in performance in inexperienced users, they can have unintended and/or paradoxical behavioural effects on experienced users.
Posterior Analysis for Normalized Random Measures with Independent Increments
Authors: JAMES LANCELOT F. , LIJOI ANTONIO , PRÜNSTER IGOR
Published: July 2008

Abstract. One of the main research areas in Bayesian Nonparametrics is the proposal and study of priors which generalize the Dirichlet process. In this paper, we provide a comprehensive Bayesian non‐parametric analysis of random probabilities which are obtained by normalizing random measures with independent increments (NRMI). Special cases of these priors have already shown to be useful for statistical applications such as mixture models and species sampling problems. However, in order to fully exploit these priors, the derivation of the posterior distribution of NRMIs is crucial: here we achieve this goal and, indeed, provide explicit and tractable expressions suitable for practical implementation. The posterior distribution of an NRMI turns out to be a mixture with respect to the distribution of a specific latent variable. The analysis is completed by the derivation of the corresponding predictive distributions and by a thorough investigation of the marginal structure. These results allow to derive a generalized Blackwell–MacQueen sampling scheme, which is then adapted to cover also mixture models driven by general NRMIs.
Soap Film Smoothing
Authors: Wood Simon N. , Bravington Mark V. , Hedley Sharon L.
Published: July 2008

Conventional smoothing methods sometimes perform badly when used to smooth data over complex domains, by smoothing inappropriately across boundary features, such as peninsulas. Solutions to this smoothing problem tend to be computationally complex, and not to provide model smooth functions which are appropriate for incorporating as components of other models, such as generalized additive models or mixed additive models. We propose a class of smoothers that are appropriate for smoothing over difficult regions of R2 which can be represented in terms of a low rank basis and one or two quadratic penalties. The key features of these smoothers are that they do not ‘smooth across’ boundary features, that their representation in terms of a basis and penalties allows straightforward incorporation as components of generalized additive models, mixed models and other non-standard models, that smoothness selection for these model components is straightforward to accomplish in a computationally efficient manner via generalized cross-validation, Akaike's information criterion or restricted maximum likelihood, for example, and that their low rank means that their use is computationally efficient.
QUANTIFYING THE LAFFER CURVE ON THE CONTINUED ACTIVITY TAX IN A DYNASTIC FRAMEWORK*
Authors: Hairault Jean‐Olivier , Langot François , Sopraseuth Thepthida
Published: July 2008

It is argued that the tax on continued activity should be removed by implementing actuarially fair schemes. However, these schemes cannot fund the expected Social Security (SS) deficit. This article proposes to give individuals a fraction of the actuarially fair incentives in the case of postponed retirement. SS faces a trade‐off between giving enough incentives to make individuals delay retirement and giving little increase in pensions in order to help finance its expected deficit. This trade‐off is captured by a Laffer curve. Finally, when the SS system aims to maximize welfare, the optimal tax on postponed retirement is still strictly positive.
IMPLEMENTATION CYCLES, INVESTMENT, AND GROWTH*
Authors: Francois Patrick , Lloyd‐Ellis Huw
Published: July 2008

We develop a model of “intrinsic” cycles, driven by the decentralized behavior of entrepreneurs and firms making continuous, divisible improvements in their productivity. We show that when the introduction of productivity improvements is endogenous, implementation cycles arise even in the presence of reversible investment and consumption smoothing. The implied cyclical equilibrium is unique within its class and shares several features in common with actual business cycles. In particular, its predictions are qualitatively consistent with the joint behavior of the investment rate and Tobin's Q during U.S. recessions.
A THEORY OF WAGES AND LABOR DEMAND WITH INTRA‐FIRM BARGAINING AND MATCHING FRICTIONS*
Authors: Cahuc Pierre , Marque Francois , Wasmer Etienne
Published: July 2008

This article provides a model of labor market equilibrium with search and within‐firm strategic bargaining. We yield explicit closed form solutions with heterogeneous labor inputs and capital. The solution exhibits overemployment. We show that higher relative bargaining power for some groups of workers may lead to overemployment relative to other groups, with such other groups being underemployed instead if they have a lower relative bargaining power. Similarly, the hold‐up problem between capitalists and employees does not necessarily lead to underinvestment in physical capital.
PILL, PATCH, OR SHOT? SUBJECTIVE EXPECTATIONS AND BIRTH CONTROL CHOICE*
Authors: Delavande Adeline
Published: July 2008

When choosing a contraception method, women base their decisions on their subjective expectations about the realizations of method‐related outcomes. Examples of outcomes include getting pregnant and contracting a sexually transmitted disease (STD). I combine innovative data on probabilistic expectations with observed contraceptive choices to estimate a random utility model of birth control choice. The availability of expectations data is essential to identify preferences from beliefs. Effectiveness, protection against STDs, and partner's disapproval are found to be the most important factors in the decision process. The elicited expectations and inferred preference parameters are used to simulate the impact of various policies.
CHOOSY SEARCH AND THE MISMATCH OF TALENTS*
Authors: Decreuse Bruno
Published: July 2008

This article proposes a multi‐sector matching model where workers have (symmetric) sector‐specific skills and the search market is segmented by sector. Workers choose the range of markets they are willing to participate in. I identify a composition externality: Workers do not take into account the impact of their choice on sector‐specific mean productivity among the pools of job‐seekers. Consequently, workers prospect too many market segments, and there is room for public policy even when the so‐called Hosios condition holds.
Augmentation of serotonin release by sustained exposure to MDMA and methamphetamine in rat organotypic mesencephalic slice cultures containing raphe serotonergic neurons
Authors: Higuchi Megumi , Suzuki Yuichi , Yatani Yumi , Kitagawa Yutaka , Nagayasu Kazuki , Shirakawa Hisashi , Nakagawa Takayuki , Kaneko Shuji
Published: July 2008

Several lines of evidence suggest the involvement of the raphe‐serotonergic neurons in addiction to psychostimulants and some recreational drugs. In this study, we established rat organotypic mesencephalic slice cultures containing the raphe nuclei and examined the effects of sustained exposure to 3,4‐methylenedioxymethamphetamine (MDMA) and methamphetamine (METH). Immunostaining for tryptophan hydroxylase (TPH) studies revealed that serotonergic neurons were abundant in the slice cultures. Sustained exposure to MDMA and METH (1–1000 μM) for 4 days had little effect on the serotonin tissue content, [3H]citalopram binding, or expression/phosphorylation of TPH. Treatment with MDMA or METH for 30 min increased serotonin release in a concentration‐dependent manner. Slice cultures were exposed to MDMA for 4 days following a 1‐day withdrawal period and then challenged with MDMA (10 μM). Sustained MDMA exposure augmented MDMA‐induced serotonin release in a concentration‐dependent manner, indicating serotonergic sensitization. Similar serotonergic sensitization was observed for METH. The development of MDMA‐induced serotonergic sensitization was attenuated by the NMDA receptor antagonist, MK‐801 (10 μM). These results suggest that in mesencephalic slice cultures sustained MDMA or METH exposure induces serotonergic sensitization through activation of NMDA receptors without serotonergic neurotoxicity. The in vitro model system could help to elucidate the mechanisms underlying drug addiction.
Anticonvulsant effects of linolenic acid are unrelated to brain phospholipid cell membrane compositions
Authors: Porta Natacha , Bourgois Béatrice , Galabert Claude , Lecointe Cécile , Cappy Pierre , Bordet Régis , Vallée Louis , Auvin Stéphane
Published: July 2008

Purpose:  Recent studies have revealed that polyunsaturated fatty acids (PUFAs) have anticonvulsive properties. Clinical trials using PUFAs reported conflicting results. It was suggested that PUFAs have anticonvulsant effects via modifications of brain phospholipids. Moreover, some authors suggested that the effect of the ketogenic diet (KD) leads to a high PUFA content. The aim of the study was to evaluate the anticonvulsant properties of a mixture containing α‐linolenic acid (ALA) and linolenic acid (LA).

Methods:  Four‐week‐old male Wistar rats were fed one of the following diets for 30 days: KD, standard diet, and standard diet with daily LA/ALA oral supplementation. Pentylenetetrazol (PTZ) threshold was used to assess the anticonvulsive effects of the diets. Nutritional status was monitored by body composition evaluation. Fatty acids composition of both plasma and brain phospholipids were also assessed.

Results:  Animals fed the KD and those who had the daily LA/ALA supplementation exhibited an increase in PTZ threshold. The animals did not show any modification of body composition or brain phospholipid composition. The plasma fatty acids composition was modified by KD and LA/ALA. A decrease in arachidonic acid (AA) concentrations was observed in both the KD and LA/ALA groups, while an increase in eicosapentanoic acid (EPA) and ALA concentrations was only observed in the LA/ALA group.

Conclusions:  Our study shows that LA/ALA supplementation exerts anticonvulsive properties comparable to KD. Nutritional status can not explain the anticonvulsive effects of PUFAs supplementation. Brain phospholipids were not different within groups. The anticonvulsive effects of LA supplementation seem to be unrelated to brain phospholipid composition.
Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: Implications for autism and epilepsy
Authors: Gant John C. , Thibault Oliver , Blalock Eric M. , Yang Jun , Bachstetter Adam , Kotick James , Schauwecker Paula E. , Hauser Kurt F. , Smith George M. , Mervis Ron , Li YanFang , Barnes Gregory N.
Published: July 2008

Purpose:  Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins have been implicated in guidance, migration, differentiation, and synaptic plasticity of neurons. The semaphorin 3F (Sema3F) ligand and its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 signaling may intimately direct the apposition of presynaptic and postsynaptic locations, facilitating the development and maturity of hippocampal synaptic function. To further understand the role of NPN2 signaling in central nevous system (CNS) plasticity, structural and functional alterations were assessed in NPN2 deficient mice.

Methods:  In NPN2 deficient mice, we measured seizure susceptibility after kainic acid or pentylenetetrazol, neuronal excitability and synaptic throughput in slice preparations, principal and interneuron cell counts with immunocytochemical protocols, synaptosomal protein levels with immunoblots, and dendritic morphology with Golgi‐staining.

Results:  NPN2 deficient mice had shorter seizure latencies, increased vulnerability to seizure‐related death, were more likely to develop spontaneous recurrent seizure activity after chemical challenge, and had an increased slope on input/output curves. Principal cell counts were unchanged, but GABA, parvalbumin, and neuropeptide Y interneuron cell counts were significantly reduced. Synaptosomal NPN2 protein levels and total number of GABAergic synapses were decreased in a gene dose‐dependent fashion. CA1 pyramidal cells showed reduced dendritic length and complexity, as well as an increased number of dendritic spines.

Discussion:  These data suggest the novel hypothesis that the Sema 3F signaling system's role in appropriate placement of subsets of hippocampal interneurons has critical downstream consequences for hippocampal function, resulting in a more seizure susceptible phenotype.
Dose‐dependent anticonvulsant effects of linoleic and α‐linolenic polyunsaturated fatty acids on pentylenetetrazol induced seizures in rats
Authors: Taha Ameer Y. , Filo Elvis , Ma David W. L. , McIntyre Burnham W.
Published: July 2008

Purpose:  Linoleic and α‐linolenic polyunsaturated fatty acids, derived from plant oils, have been reported to reduce neuronal excitability ex vivo and in cell culture. The evidence derived from animal seizure models, however, has been contradictory. The goal of the present study was to assess the dose‐dependent anticonvulsant effects of a fatty acid mixture containing linoleic and α‐linolenic acids in a 4 to 1 ratio (the “SR‐3” compound).

Methods:  The maximal pentylenetetrazol seizure model and Long‐Evans hooded rats were used.

Results:  Daily intraperitoneal injection of SR‐3 for 21 consecutive days raised omega‐3 polyunsaturated fatty acid (n‐3 PUFA) composition in the unesterified fatty acid fraction of brain lipids (p  < 0.05), and increased latency to seizure onset when administered at 200  mg/kg (p < 0.05), but not at 40  mg/kg (p > 0.05). There were no significant effects of SR‐3 on seizure occurrence or on seizure severity (p > 0.05). A toxic effect of the SR‐3 compound on peristalsis was observed at a dose of 400  mg/kg and above.

Conclusion:  Linoleic and α‐linolenic polyunsaturated fatty acids in a 4 to 1  ratio raises n‐3 PUFA composition of unesterified fatty acids in the brain and increases resistance to pentylenetetrazol‐induced seizures.
Validity of Pain Behaviors in Persons with Mild to Moderate Cognitive Impairment
Authors: Shega Joseph W. , Rudy Thomas , Keefe Francis J. , Perri Lisa Caitlin , Mengin Olga Telgarska , Weiner Debra K.
Published: July 2008

OBJECTIVES: To evaluate the validity of traditional pain behaviors (guarding, bracing, rubbing, grimacing, and sighing) in persons with and without cognitive impairment and chronic low back pain (CLBP).

DESIGN: Prospective observational study.

SETTING: Outpatient clinics.

PARTICIPANTS: Thirty‐seven cognitively intact and 40 cognitively impaired participants with and without CLBP.

MEASUREMENTS: Frequency of traditional pain behaviors.

RESULTS: Forty‐six of the participants were pain free, and 31 had CLBP. The internal consistency reliability coefficient of the five pain behaviors was 0.32, suggesting that a unidimensional scale did not exist. Multivariate analysis of variance analysis according to the independent variables pain status (pain free vs CLBP) and cognitive status (intact vs impaired) with the dependent variable frequency of pain behaviors found significant differences according to pain status (F[5,61]=3.06, P=.02) and cognitive status (F[5,61]=5.41, P<.001) but without evidence of an interaction (F[5,61]=1.14, P=.35). Participants with CLBP exhibited significantly higher levels of grimacing (P<.001) and guarding (P=.02) than pain‐free participants. Intact subjects exhibited fewer guarding (P=.02) and rubbing behaviors (P<.001) but a higher number of bracing behaviors (P=.03) than cognitively impaired participants.

CONCLUSION: These results support the utility of facial grimacing in assessing pain in patients with mild to moderate cognitive impairment and call into question the validity of guarding and rubbing in assessing pain in persons with mild to moderate cognitive impairment.
Fabrication of (K,Na)NbO3Lead‐Free Piezoceramic Microrod Arrays by Sol–Gel Processing with Micromachined Silicon Templates
Authors: Xu Ying , Liu Dawei , Lai Fengping , Zhen Yuhua , Li Jing‐Feng
Published: July 2008

A microfabrication process combining sol–gel processing and silicon micromolding was proposed to fabricate microrod arrays of K0.5Na0.5NbO3(KNN) lead‐free piezoelectric ceramics. By ultraviolet lithography and inductively coupled plasma deep reactive ion etching, a Si mold with a regular array of columnar cavities was micromachined, and then filled with KNN sol, followed by pyrolysis and annealing treatment. By optimizing the processing conditions, KNN ceramic microrod arrays of 15 μm lateral width, 30 μm height, and 70 μm spacing were produced, which were identified as perovskite phase structure by X‐ray diffraction.
Aminolaevulinic acid diffusion characteristics in ‘in vitro’ normal human skin and actinic keratosis: implications for topical photodynamic therapy
Authors: McLoone Nabla , Donnelly Ryan F. , Walsh Maureen , Dolan Olivia M. , McLoone Sean , McKenna Kevin , McCarron Paul A.
Published: July 2008

Background: The response rate of aminolaevulinic acid (ALA)‐based photodynamic therapy (PDT) in certain subtypes of actinic keratosis (AK), such as hypertrophic and hyperkeratotic lesions, is variable, an effect attributable to a supposed lack of ALA penetration. A detailed and depth‐related profile of spatial ALA permeation in AK following drug administration would lead to a greater understanding of concentrations achievable before protoporphyrin IX biosynthesis and subsequent PDT.

Methods: ALA penetration through excised normal human skin (NS) and AK lesions was evaluated using a cryostatic sectioning technique and radio‐isotope counting following drug delivery using a novel, bioadhesive patch, loaded with 19, 38 or 50 mg/cm2 ALA.

Results: Distinct differences in ALA concentration with respect to depth between AK and NS samples were shown, particularly within the superficial layers of the tissue structure, down to a depth of 1.0 mm. Patch application times were shown to influence ALA concentrations in tissue, but there was no clear correlation between ALA penetration in AK lesions taken from different body locations and from patients of different age. Similarly, the thickness of stratum corneum was not related to the ALA distribution profiles.

Conclusions: Sizable variation in ALA concentration was a prominent feature of profiles through AK lesions, which may explain the variation of observed protoporphyrin IX production seen in the clinical implementation of AK PDT. That said, the results of this study show sufficient ALA penetration to a depth of 1.0 mm, which should be satisfactory for successful treatment of the majority of non‐hyperkeratotic, hypertrophic AK using patch‐based delivery methods.
Molecular responses of the Ts65Dn and Ts1Cje mouse models of Down syndrome to MK‐801
Authors: Siddiqui A. , Lacroix T. , Stasko M. R. , Scott‐McKean J. J. , Costa A. C. S. , Gardiner K. J.
Published: July 2008

Down syndrome (DS), caused by trisomy of human chromosome 21 (chr21), is the most common genetic cause of intellectual disability. The Ts65Dn mouse model of DS is trisomic for orthologs of 94 chr21‐encoded, confirmed protein‐coding genes and displays a number of behavioral deficits. Recently, Ts65Dn mice were shown to be hypersensitive to the locomotor stimulatory effects of the high‐affinity N‐methyl‐d‐aspartate (NMDA) receptor (NMDAR) channel blocker, MK‐801. This is consistent with the functions of several chr21 proteins that are predicted directly or indirectly to impact NMDAR function or NMDAR‐mediated signaling. In this study, we show that a second mouse model of DS, the Ts1Cje, which is trisomic for 70 protein‐coding genes, is also hypersensitive to MK‐801. To investigate the molecular basis for the responses to MK‐801, we have measured levels of a subset of chr21 and phosphorylated non‐chr21 proteins, in the cortex and hippocampus of Ts65Dn and Ts1Cje mice and euploid controls, with and without treatment with MK‐801. We show that in euploid mice, the chr21‐encoded proteins, TIAM1 and DYRK1A, and phosphorylation of AKT, ERK1/2 and the transcription factor ELK are involved in the MK‐801 response. However, in both Ts65Dn and Ts1Cje mice, levels of phosphorylation are constitutively elevated in naïve, unstimulated mice, and the MK‐801‐induced changes in TIAM1 and DYRK1A and in phosphorylation are either absent or abnormal, with both genotype and brain‐region‐specific patterns. These results emphasize the complexities of the pathway perturbations that arise with segmental trisomy.
Factors Influencing Independence in Adolescents With Sickle Cell Disease
Authors: Newland Jamesetta A.
Published: July 2008

PROBLEM:  Factors that predict successful transition from pediatric to adult care for adolescents with sickle cell disease are not fully understood, making transfer decisions difficult.

METHODS:  Seventy‐four adolescents (14–21 years) participated in this descriptive correlational study to investigate the relationships of age, gender, knowledge about sickle cell disease, disease severity, and family relationships to independence.

FINDINGS:  Knowledge, severity, and family relationships explained only 25% of the variance for independence in the final model; family relationships were inversely correlated.

CONCLUSIONS:  Factors exerting stronger influences on independence remain unknown. Cultural factors may be important among this predominantly African American population.