bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Amino Acid Substitutions in Transmembrane Domains of the NR1 Subunit on the Ethanol Inhibition of RecombinantN‐Methyl‐d‐aspartate Receptors
Authors: Thetford Smothers C. , Woodward John J.
Published: February 2006

Background:TheN‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptor is involved in a variety of processes that regulate neuronal plasticity and is an important target for the acute and chronic effects of ethanol. However, the specific sites where ethanol interacts with the receptor protein have yet to be fully elucidated. We previously demonstrated that a phenylalanine to alanine mutation in the third transmembrane domain (TM3) of the NR1 subunit decreased the ethanol inhibition of NMDA receptors expressed in HEK293 cells. In this study, we characterized the ethanol inhibition of NMDA receptors containing additional mutations within the TM3 and TM4 domains of the NR1 subunit.

Methods:Site‐directed mutagenesis was used to alter specific amino acid residues in the TM3 and TM4 domains of the NR1 subunit. Mutant NR1 subunits were coexpressed with the NR2A subunit in HEK293 cells and examined for alterations in ethanol sensitivity using whole‐cell voltage‐clamp electrophysiology.

Results:Replacing phenylalanine at TM3 position 639 in the NR1 subunit (F639) with 9 different amino acids produced functional receptors when coexpressed with the NR2A subunit. All mutants showed a concentration‐dependent inhibition by ethanol (10–100 mM), with the alanine and serine mutants being significantly less sensitive to ethanol. Amino acid substitutions at the F639 site also produced variable changes in the concentration–response relationship to glycine. However, no significant correlation between glycine EC50values and the magnitude of ethanol inhibition was observed. Alanine mutations at TM4 positions 813 (M813A) and 819 (L819A), but not at 817 (F817A), of the NR1 subunit enhanced ethanol inhibition. Substitution of tryptophan for TM4 residues in the NR1 subunit (positions 820–822) that are homologous to a site in the NR2A subunit shown to reduce ethanol inhibition (A825W) had no effect on ethanol sensitivity. However, these NR1 TM4 tryptophan mutants restored the ethanol inhibition of the NR1 TM3 F639A mutant to wild‐type levels in a stepwise fashion.

Conclusions:These results indicate that the ethanol sensitivity of NMDA receptors may be regulated by discrete sites within the TM3 and TM4 domains of the NR1 subunit.
Brain Metabolite Concentrations and Neurocognition During Short‐term Recovery from Alcohol Dependence: Preliminary Evidence of the Effects of Concurrent Chronic Cigarette Smoking
Authors: Durazzo Timothy C. , Gazdzinski Stefan , Rothlind Johannes C. , Banys Peter , Meyerhoff Dieter J.
Published: February 2006

Background: Longitudinal studies of brain tissue metabolite recovery in short‐term abstinent alcoholics have primarily investigated the frontal lobes and cerebellum with variable results. Preliminary proton magnetic resonance spectroscopic imaging (1H MRSI) suggested that chronic cigarette smoking exacerbates alcohol‐induced brain injury in 1‐week abstinent alcoholics. However, the potential effects of chronic cigarette smoking on the recovery of alcohol‐induced brain injury have not been studied.

Methods: Multislice short‐echo time 1H MRSI was used to measure longitudinal changes in common brain metabolites in 25 recovering alcohol‐dependent individuals (RA), retrospectively assigned to smoking (n=14) and nonsmoking (n=11) subgroups. Recovering alcohol‐dependent individuals in longitudinal analyses were studied after approximately 7 and 34 days of abstinence from alcohol. In cross‐sectional analyses, 36 RA (19 smokers, 17 nonsmokers) with approximately 34 days of sobriety were compared with 29 light drinkers (LD). Relationships between neurocognition and metabolite concentrations in abstinent RA were also examined.

Results: Over 1 month of abstinence from alcohol, RA, as a group, showed significant increases of regional N‐acetylaspartate (NAA; marker of neuronal viability) and choline‐containing compounds (Cho; marker of cell membrane synthesis/turnover) primarily in frontal and parietal lobes. These increases appeared to be driven by nonsmoking RA. Cross‐sectional results indicate that metabolite levels in RA at 35 days of sobriety are not significantly different from those in LD in most regions, except for lower NAA and Cho in parietal WM and subcortical structures. However, metabolite levels at that time appear to be strongly modulated by smoking status. The patterns of metabolite–neurocognition relationships were different for nonsmoking and smoking RA.

Conclusions: Within the first weeks of sobriety, regional brain NAA and Cho levels increased, but metabolite levels did not normalize in all brain regions after 35 days of sobriety. Neurobiologic recovery in RA appeared to be adversely affected by chronic smoking. Greater consideration of the effects of continued cigarette smoking on the neurobiologic and neurocognitive recovery of alcohol‐dependent individuals is warranted.
Fatty Acid Ethyl Esters in Human Mononuclear Cells: Production by Endogenous Synthesis Greatly Exceeds the Uptake of Preformed Ethyl Esters
Authors: Alhomsi Khaled , Cluette‐Brown Joanne E. , Laposata Michael
Published: February 2006

Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol‐induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins.

Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE‐associated fatty acid upon FAEE hydrolysis.

Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08–120 minutes, and FAEE uptake and hydrolysis were measured.

Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate.

Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.
The Alcohol Content of Wine Consumed in the US and Per Capita Consumption: New Estimates Reveal Different Trends
Authors: Kerr William C. , Greenfield Thomas K. , Tujague Jennifer , Brown Stephan E.
Published: February 2006

Background:To estimate the mean percentage alcohol content by volume (%ABV) for wine sold in the US and in each state for the years 1962 to 2002, and to apply these to per capita wine sales for the years 1970 to 2002.

Method:Estimates of wine‐type mean %ABV are calculated using brand‐level sales and %ABV from one state and are extrapolated to other states and to the US using wine‐type sales.

Results:The mean %ABV is found to vary substantially over time and across states, with US means ranging from 16.2% in 1962 to a low of 10.5% in 1991. By 2002, the US mean %ABV had risen to nearly 11.5%. Application of %ABV estimates to the per capita consumption of wine indicated significant differences from previous estimates with lower alcohol intake from wine found for all years after 1980 and 6 year‐to‐year changes in opposite directions.

Conclusions:Empirically based estimates of the alcohol content of wine sold in the US show changes over time and differences between states that have significance for epidemiologic monitoring and modeling of the determinants and consequences of alcohol use and for improving comparisons with per capita beer and spirits consumption series.
The Effect of the Real Option to Transfer on the Value of Guaranteed Minimum Death Benefits
Authors: Ulm Eric R.
Published: February 2006

Abstract

Variable annuity contracts frequently have many options and option‐like features embedded in the contracts. Some are obvious, such as guaranteed minimum death benefits (GMDBs), while others are less obviously option‐like. In this article, we consider the effect of the real option to transfer funds between fixed and variable accounts. If a GMDB rider is considered in isolation, it is sometimes in the policyholder's interest to transfer to the fixed fund if the fixed fund earns less than the variable fund in a risk‐neutral world. On the other hand, the option to transfer will not be used if the entire annuity and rider are considered together.
Guarantees in With‐Profit and Unitized With‐Profit Life Insurance Contracts: Fair Valuation Problem in Presence of the Default Option
Authors: Ballotta Laura , Haberman Steven , Wang Nan
Published: February 2006

Abstract

The purpose of the article is to apply contingent claim theory to the valuation of the type of participating life insurance policies commonly sold in the UK. The article extends the techniques developed by Haberman, Ballotta, and Wang (2003) to allow for the default option. The default option is a feature of the design of these policies, which recognizes that the insurance company's liability is limited by the market value of the reference portfolio of assets underlying the policies that have been sold. The valuation approach is based on the classical contingent claim pricing “machinery,” underpinned by Monte Carlo techniques for the computation of fair values. The article addresses in particular the issue of a fair contract design for a complex type of participating policy and analyzes in detail the feasible set of policy design parameters that would lead to a fair contract and the trade‐offs between these parameters.
Can Bonus‐Malus Allieviate Insurance Fraud?
Authors: Moreno Ignacio , Vázquez Francisco J. , Watt Richard
Published: February 2006

Abstract

Traditionally, insurance companies attempt to reduce (or even eliminate) fraud via audit strategies under which claims may be investigated at some cost to the insurer, with a penalty imposed upon insureds who are found to report claims fraudulently. However, it is also clear that, in a multiperiod setting, bonus‐malus contracts (increases in subsequent premiums whenever a claim is presented) also provide an incentive against fraud. In this article, we consider a model in which, conditional upon the client renewing his contract, the only mechanism used to combat fraud is bonus‐malus. In this way, our model provides the opposite pole to the pure audit model. We show that in our simplified setting there exists a bonus‐malus contract that will eliminate all fraud in all periods, while guaranteeing nonnegative expected profits to the insurer and participation by the insured. We also consider the dynamics of the solution, the effect of an increase in risk aversion on the solution, and the welfare implications.
Does Reinsurance Need Reinsurers?
Authors: Plantin Guillaume
Published: February 2006

Abstract

The reinsurance market is the secondary market for insurance risks. It has a very specific organization. Direct insurers rarely trade risks with each other. Rather, they cede part of their primary risks to specialized professional reinsurers who have no primary business. This article offers a model of equilibrium in reinsurance and capital markets in which professional reinsurers arise endogenously. Their role is to monitor primary insurers credibly, so that insurers can raise capital more easily. In equilibrium, the financial structure of primary insurers consists of a mix of reinsurance and outside capital. The comparative statics yield empirical predictions which are broadly in line with a number of stylized facts from the reinsurance market.
Romanticism and War
Authors: Ramsey Neil
Published: February 2006

This article examines recent Romantic scholarship that has begun to explore the connections between British Romantic period writing and the French Revolutionary and Napoleonic Wars. Countering traditional views that writers were largely unconcerned with the events of these wars, such scholarship has argued that the wars had a significant impact on the writing of the period. Though some critics have viewed the period's writers as unquestioningly reproducing the wars as an exciting spectacle, others have drawn attention to the ways in which the meanings of war were contested through the period. Particularly central to these discussions has been the issue of suffering and the extent to which such suffering was either foregrounded or rhetorically elided from the public's view. The article concludes by looking at some of the most recent trends in this scholarship.
“The Sun Shines on a World Re‐Arisen to Pleasure”: The Fin‐de‐Siècle Metaphysical Revival
Authors: Seeley Tracy
Published: February 2006

The 1890s witnessed an explosion of interest in the metaphysical and other seventeenth‐century poets, a fact that warrants further scholarly exploration. This article outlines the background of the revival: the cultural and religious politics that shape mid‐century commentary on the metaphysicals, and Coleridge's marginalia which rehabilitate the poets, especially Donne. It then presents an overview of criticism by Gosse, Symons, Meynell, Thompson, and Johnson, tracing the similarities and differences among aesthetic and decadent visions of the seventeenth century. Finally, it suggests a number of areas for new work on the topic.
Access and Agency in Elizabeth Cary's The Tragedy of Mariam: Early Modern Closet Drama and the Spatialization of Power1
Authors: Mejia‐LaPerle Carol
Published: February 2006

This essay was runner‐up in the 2005 Literature Compass Graduate Essay Prize, Renaissance Section.

Numerous critics have explored the stoic sentiments in Elizabeth Cary's The Tragedy of Mariam (1613), especially the ways in which female characters negotiate the demands of patriarchal force, while expressing a conscience contrary to those demands. However, this essay examines the material conditions necessary for pursuing stoic ideals, prompted by the fact that Cary uniquely depicts female resistance of tyrannical conditions in distinctly spatial terms. Her closet drama consistently deploys literary representations of space to ask important questions about gendered subjects: How is space an expression and enforcement of power upon women? How can spatial configurations be manipulated to alter or circumvent the effects of tyranny? This essay argues that Cary's closet drama depicts power as a force that organizes environments; that is, spatial arrangements that regulate characters’ behaviors are also the material manifestations of authority through which the discourses expressing female agency are constructed and contained. Since closet dramas were not written for public performance but for consumption within a domestic setting, spatial arrangements are apprehended through, indeed are never prior to, the act of reading. The reader perceives the play's landscape – the play's space – through the characters’ language. This study tests the reciprocity between space and words, specifically the way spatialization in the play facilitates the processes and practices of female speech.
“I Can neither Write nor Be Silent:” The Circulation of Women's Texts in Sidney's Old Arcadia*
Authors: Ghita Lucian
Published: February 2006

This essay won the 2005 Literature Compass Graduate Essay Prize, Renaissance Section.

The production, circulation, and reception of women's texts in early modern Europe probe important questions about the status of women as writers of public influence within a male‐dominated manuscript and print culture. Insofar as it foregrounds the semiotic exchanges between author, text, and reader in Phillips Sydney's Old Arcadia, Derrida's concept of supplementarity opens up new ways of interpreting the political and gender economy of Sidney's language in relation to the socio‐cultural positions of women in early modern England. The Old Arcadia presents several scenes in which women, specifically Pamela, use writing as a self‐reflective mode of negotiating a position of authority within an unstable semiotic space.
THIS ARTICLE HAS BEEN RETRACTED Katherine Philips's Politicised Coterie Writing
Authors: Kirschbaum Robin
Published: February 2006

This essay was runner‐up in the 2005 Literature Compass Graduate Essay Prize, Seventeenth Century Section.

Private epistolary exchange took place as part of a more encompassing social exchange in the early modern period. For a royalist such as Katherine Philips, coterie exchange was a conscious means of creating and maintaining a sympathetic literary community based on common ideology. Philips's coterie production, spanning her socially isolated time in both Wales and Ireland, represents not only an attempt to further individual literary reputation, but as an enabling space from which to form a community of ideologically minded individuals. Such coterie production can be seen as a dynamic construction of a public space as an alternative site of power. Drawing from the Habermasian model of the literary public sphere and Hannah Arendt's notion of public space, I argue that the politicised coterie overturns the binaries of author/reader, manuscript/print, and public/private, offering strategies for royalist women writers to enter into a public discourse from within a ‘private’ production and circulation. Replacing the historical narratives of the political uprisings of the 1650s with narratives of heroism and friendship, Philips's coterie is not necessarily a retreat from a troubled social and political atmosphere, but a refiguring of the heroic and social traditions of Royalists from within a contemporary position of exile and isolation. Philips's poetry of female friendship is not only a response to the separation and loss of the Civil War, but an active construction of an alternative community based upon politicised friendship. Writing in a period of change and in the face of personal isolation, friendships based on literary exchange constituted an alternative society in which the participants imaginatively shed the differences which separate them in the larger, public world. Examining the coterie verse and epistolary writing of Katherine Philips in the context of an alternative political community reveals the need for renewed critical focus upon collectivities and alliances which shaped early modern women's writing.
Short gamma-ray bursts in old populations: magnetars from white dwarf—white dwarf mergers
Authors: Levan Andrew J. , Wynn Graham A. , Chapman Robert , Davies Melvyn B. , King Andrew R. , Priddey Robert S. , Tanvir Nial R.
Published: February 2006

Recent progress on the nature of short-duration gamma-ray bursts has shown that a fraction of them originate in the local Universe. These systems may well be the result of giant flares from soft gamma-repeaters (highly magnetized neutron stars commonly known as magnetars). However, if these neutron stars are formed via the core collapse of massive stars then it would be expected that the bursts should originate from predominantly young stellar populations, while correlating the positions of BATSE short bursts with structure in the local Universe reveals a correlation with all galaxy types, including those with little or no ongoing star formation. This is a natural outcome if, in addition to magnetars formed via the core collapse of massive stars, they also form via accretion-induced collapse following the merger of two white dwarfs, one of which is magnetic. We investigate this possibility and find that the rate of magnetar production via white dwarf–white dwarf (WD–WD) mergers in the Milky Way is comparable to the rate of production via core collapse. However, while the rate of production of magnetars by core collapse is proportional to the star formation rate, the rate of production via WD–WD mergers (which have long lifetimes) is proportional to the stellar mass density, which is concentrated in early-type systems. Therefore magnetars produced via WD–WD mergers may produce soft gamma-repeater giant flares which can be identified with early-type galaxies. We also comment on the possibility that this mechanism could produce a fraction of the observed short-duration burst population at higher redshift.
The infrared glow of the first stars
Authors: Salvaterra Ruben , Magliocchetti Manuela , Ferrara Andrea , Schneider Raffaella
Published: February 2006

Kashlinsky et al. find a significant cosmic infrared background fluctuation excess on angular scales ≳50 arcsec that cannot be explained by instrumental noise or local foregrounds. The excess has been tentatively attributed to emission from primordial, very massive (Population III, hereafter PopIII) stars formed ≤ 200 Myr after the Big Bang. Using an evolutionary model motivated by independent observations and including various feedback processes, we find that PopIII stars can contribute <40 per cent of the total background intensity (νJν∼ 1–2 nW m−2 sr−1 in the 0.8–8 μm range) produced by all galaxies (hosting both PopIII and PopII stars) at z≥ 5. The infrared fluctuation excess is instead very precisely accounted for by the clustering signal of galaxies at z≥ 5, predominantly hosting PopII stars with masses and properties similar to the present ones.
Near-infrared spectroscopy of a young super-star cluster in NGC 6946: chemical abundances and abundance patterns
Authors: Larsen S. S. , Origlia L. , Brodie J. P. , Gallagher J. S.
Published: February 2006

Using the NIRSPEC spectrograph at Keck II, we have obtained H- and K-band echelle spectra for a young (∼10–15 Myr), luminous (MV∼−13.2) super-star cluster in the nearby spiral galaxy NGC 6946. From spectral synthesis and equivalent width measurements we obtain for the first time accurate abundances and abundance patterns in an extragalactic super-star cluster. We find [Fe/H]=−0.45 ± 0.08 dex, an average α-enhancement of ≈+0.22 ± 0.1 dex, and a relatively low 12 C/13 C ≈ 8 ± 2 isotopic ratio. We also measure a velocity dispersion of ≈9.1 km s−1, in agreement with previous estimates. We conclude that integrated high-dispersion spectroscopy of massive star clusters is a promising alternative to other methods for abundance analysis in extragalactic young stellar populations.
Upper limits on the central black hole masses of 47 Tuc and NGC 6397 from radio continuum emission
Authors: De Rijcke S. , Buyle P. , Dejonghe H.
Published: February 2006

We present upper limits on the masses of the putative central intermediate-mass black holes in two nearby Galactic globular clusters: 47 Tuc (NGC 104), the second brightest Galactic globular cluster, and NGC 6397, a core-collapse globular cluster and, with a distance of 2.7 kpc, quite possibly the nearest globular cluster. These upper limits are obtained using a technique suggested by T. Maccarone. These mass estimates have been derived from 3σ upper limits on the radio continuum flux at 1.4 GHz, assuming that the putative central black hole accretes the surrounding matter at a rate of between 0.1 and 1 per cent of the Bondi accretion rate. For 47 Tuc, we find a 3σ upper limit of 2060–670 M⊙, depending on the actual accretion rate of the black hole and the distance to 47 Tuc. For NGC 6397, which is closer to us, we derive a 3σ upper limit of 1290–390 M⊙. While estimating mass upper limits based on radio continuum observations requires making assumptions about the gas density and the accretion rate of the black hole, their derivation does not require complex and time-consuming dynamical modelling. Thus, this method offers an independent way of estimating black hole masses in nearby globular clusters. If, generally, central black holes in stellar systems accrete matter faster than 0.1 per cent of the Bondi accretion rate, then these results indicate the absence of black holes in these globular clusters with masses as predicted by the extrapolated M•–σc relation.
The Determinants of Being Unbanked for U.S. Immigrants
Authors: RHINE SHERRIE L. W. , GREENE WILLIAM H.
Published: February 2006

Random‐effects binary choice models are estimated to identify the attributes that influence the likelihood that immigrants are unbanked. This study finds that the likelihood to be unbanked is higher for immigrants with less education, poverty‐level income, or a larger family but lower for immigrants with greater net worth or higher income. Among immigrant groups, Mexican and other Latin American immigrants have the highest rates of being unbanked. Programs aimed at helping immigrants move into the financial mainstream may benefit from taking into account the differences in socioeconomic attributes and migration experiences of specific populations.
Transiting to Work: The Role of Private Transportation for Low‐Income Households
Authors: GARASKY STEVEN , FLETCHER CYNTHIA NEEDLES , JENSEN HELEN H.
Published: February 2006

This study examines the role of reliable vehicles in facilitating employment, using a new data set, the Iowa Transportation and Employment Survey. The empirical results document significantly higher levels of transportation problems and human capital barriers among low‐income households compared to other households and among low‐income nonworking adults compared to their employed counterparts. The multivariate analysis of low‐income households shows that employment and reliable transportation are related. Respondents without access to a reliable vehicle are less likely to be employed; those employed are more likely to have access to a reliable vehicle. Residence in an area adjacent to a metropolitan area has a positive effect on working.
Perceived Third‐Person Effects and Consumer Attitudes on Prevetting and Banning DTC Advertising
Authors: JISU HUH , DELORME DENISE E. , REID LEONARD N.
Published: February 2006

This study examined consumer attitudes toward two potential direct‐to‐consumer (DTC) advertising regulatory options—prior approval of DTC ads and a total ban—and how those attitudes are influenced by perceived DTC ad effects and receiver‐specific characteristics within the context of the third‐person effect framework. Results suggest that (1) consumers support the prevetting of DTC ads, but not the banning of DTC ads, (2) their support for prior approval is unaffected by demographic, predispositional, and ad‐effect perceptual differences, but (3) their support for a ban is associated with age, attitude toward DTC advertising, and perceptions of negative effects on self and others.
Entertainment Industry Ratings Disclosures and the Clear and Conspicuous Standard
Authors: MARIEA GRUBBS HOY , ANDREWS J. CRAIG
Published: February 2006

This study examined entertainment ratings disclosures against the Federal Trade Commission's (FTC’s) Clear and Conspicuous Standard (CCS). In their investigation of marketing of violent entertainment to youth, the FTC advocated that the motion picture, music recording, and electronic games industries focus on “ensuring that the rating … and the reasons for the rating … are effectively and clearly communicated to parents” (p. 31). An investigation of a week of prime‐time television commercials across six networks revealed that with the exception of dual modality presentation of the letter rating, ratings disclosure information is often incomplete and falls far short of meeting the FTC's CCS. We offer recommendations to the entertainment industry to address these shortcomings.
The Provision of Trans Fat Information and Its Interaction with Consumer Knowledge
Authors: KOZUP JOHN , BURTON SCOT , CREYER ELIZABETH H.
Published: February 2006

The first significant change to the Nutrition Facts panel since its inception is the addition of trans fat information. This research examines whether this modification may have a significant effect on consumers’ disease risk perceptions and on the perceived importance of trans fat information. The results of an experiment that varied exposure to induced trans fat knowledge, trans fat levels, and Nutrition Facts Panel formats indicate that without consumer education efforts that enhance consumers’ knowledge and understanding of trans fat, effects of the new labeling regulations on consumers may be limited.
Metaphor in the Mind: The Cognition of Metaphor1
Authors: Camp Elisabeth
Published: February 2006

The most sustained and innovative recent work on metaphor has occurred in cognitive science and psychology. Psycholinguistic investigation suggests that novel, poetic metaphors are processed differently than literal speech, while relatively conventionalized and contextually salient metaphors are processed more like literal speech. This conflicts with the view of “cognitive linguists” like George Lakoff that all or nearly all thought is essentially metaphorical. There are currently four main cognitive models of metaphor comprehension: juxtaposition, category‐transfer, feature‐matching, and structural alignment. Structural alignment deals best with the widest range of examples; but it still fails to account for the complexity and richness of fairly novel, poetic metaphors.
On Sense and Direct Reference*
Authors: Caplan Ben
Published: February 2006

Millianism and Fregeanism agree that a sentence that contains a name expresses a structured proposition but disagree about whether that proposition contains the object that the name refers to (Millianism) or rather a mode of presentation of that object (Fregeanism). Various problems – about simple sentences, propositional‐attitude ascriptions, and sentences that contain empty names – beset each view. To solve these problems, Millianism can appeal to modes of presentation, and Fregeanism can appeal to objects. But this raises a further problem: namely, to explain why the proposition expressed by a sentence that contains a name matters in some cases but not in others.
Truthmakers
Authors: Rodriguez‐Pereyra Gonzalo
Published: February 2006

This bulletin contains a summary of the main topics of discussion in truthmaker theory, namely: the definition of truthmakers, problems with Truthmaker Necessitarianism and Truthmaker Maximalism, the ontological burden of truthmakers and the recalcitrant topic of truthmakers for negative truths.
Mechanical compression elicits vasodilatation in rat skeletal muscle feed arteries
Authors: Clifford Philip S. , Kluess Heidi A. , Hamann Jason J. , Buckwalter John B. , Jasperse Jeffrey L.
Published: February 2006

To date, no satisfactory explanation has been provided for the immediate increase in blood flow to skeletal muscles at the onset of exercise. We hypothesized that rapid vasodilatation is a consequence of release of a vasoactive substance from the endothelium owing to mechanical deformation of the vasculature during contraction. Rat soleus feed arteries were isolated, removed and mounted on micropipettes in a sealed chamber. Arteries were pressurized to 68 mmHg, and luminal diameter was measured using an inverted microscope. Pressure pulses of 600 mmHg were delivered for 1 s, 5 s, and as a series of five repeated 1 s pulses with 1 s between pulses. During application of external pressure the lumen of the artery was completely closed, but immediately following release of pressure the diameter was significantly increased. In intact arteries (series 1, n= 6) for the 1 s pulse, 5 s pulse and series of five 1 s pulses, the peak increases in diameter were, respectively, (mean ±s.e.m.) 16 ± 2, 14 ± 2 and 27 ± 3%, with respective times from release of pressure to peak diameter of 4.1 ± 0.3, 4.6 ± 0.7 and 2.8 ± 0.4 s. In series 2 (n= 9) the arteries increased diameter by 15 ± 2, 15 ± 2 and 30 ± 3% before and by 8 ± 1, 8 ± 1 and 21 ± 2% after removal of the endothelium with air. The important new finding in these experiments is that mechanical compression caused dilatation of skeletal muscle feed arteries with a time course similar to the change in blood flow after a brief muscle contraction. The magnitude of dilatation was not affected by increasing the duration of compression but was enhanced by increasing the number of compressions. Since removal of the endothelium reduced but did not abolish the dilatation in response to mechanical compression, it appears that the dilatation is mediated by both endothelium‐dependent and ‐independent signalling pathways.
The rate of heat storage mediates an anticipatory reduction in exercise intensity during cycling at a fixed rating of perceived exertion
Authors: Tucker Ross , Marle Trevor , Lambert Estelle V. , Noakes Timothy D.
Published: February 2006

The aim of the present study was to examine the regulation of exercise intensity in hot environments when exercise is performed at a predetermined, fixed subjective rating of perceived exertion (RPE). Eight cyclists performed cycling trials at 15°C (COOL), 25°C (NORM) and 35°C (HOT) (65% humidity throughout), during which they were instructed to cycle at a Borg rating of perceived exertion (RPE) of 16, increasing or decreasing their power output in order to maintain this RPE. Power output declined linearly in all three trials and the rate of decline was significantly higher in HOT than in NORM and COOL (2.35 ± 0.73 W min−1, 1.63 ± 0.70 and 1.61 ± 0.80 W min−1, respectively, P < 0.05). The rate of heat storage was significantly higher in HOT for the first 4 min of the trials only, as a result of increasing skin temperatures. Thereafter, no differences in heat storage were found between conditions. We conclude that the regulation of exercise intensity is controlled by an initial afferent feedback regarding the rate of heat storage, which is used to regulate exercise intensity and hence the rate of heat storage for the remainder of the anticipated exercise bout. This regulation maintains thermal homeostasis by reducing the exercise work rate and utilizing the subjective RPE specifically to ensure that excessive heat accumulation does not occur and cellular catastrophe is avoided.
Kinetics of force recovery following length changes in active skinned single fibres from rabbit psoas muscle
Authors: Burton Kevin , Simmons Robert M. , Sleep John , Simmons Robert M. , Burton Kevin , Smith David A.
Published: February 2006

Redevelopment of isometric force following shortening of skeletal muscle is thought to result from a redistribution of cross‐bridge states. We varied the initial force and cross‐bridge distribution by applying various length‐change protocols to active skinned single fibres from rabbit psoas muscle, and observed the effect on the slowest phase of recovery (‘late recovery’) that follows transient changes. In response to step releases that reduced force to near zero (∼8 nm (half sarcomere)−1) or prolonged shortening at high velocity, late recovery was well described by two exponentials of approximately equal amplitude and rate constants of ∼2 s−1 and ∼9 s−1 at 5°C. When a large restretch was applied at the end of rapid shortening, recovery was accelerated by (1) the introduction of a slow falling component that truncated the rise in force, and (2) a relative increase in the contribution of the fast exponential component. The rate of the slow fall was similar to that observed after a small isometric step stretch, with a rate of 0.4–0.8 s−1, and its effects could be reversed by reducing force to near zero immediately after the stretch. Force at the start of late recovery was varied in a series of shortening steps or ramps in order to probe the effect of cross‐bridge strain on force redevelopment. The rate constants of the two components fell by 40–50% as initial force was raised to 75–80% of steady isometric force. As initial force increased, the relative contribution of the fast component decreased, and this was associated with a length constant of about 2 nm. The results are consistent with a two‐state strain‐dependent cross‐bridge model. In the model there is a continuous distribution of recovery rate constants, but two‐exponential fits show that the fast component results from cross‐bridges initially at moderate positive strain and the slow component from cross‐bridges at high positive strain.
Kinetic, pharmacological and activity‐dependent separation of two Ca2+ signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones
Authors: Canepari Marco , Ogden David
Published: February 2006

Type 1 metabotropic glutamate receptors (mGluR1) in Purkinje neurones (PNs) are important for motor learning and coordination. Here, two divergent mGluR1 Ca2+‐signalling pathways and the associated membrane conductances were distinguished kinetically and pharmacologically after activation by 1‐ms photorelease of l‐glutamate or by bursts of parallel fibre (PF) stimulation. A new, mGluR1‐mediated transient K+ conductance was seen prior to the slow EPSC (sEPSC). It was seen only in PNs previously allowed to fire spontaneously or held at depolarized potentials for several seconds and was slowly inhibited by agatoxin IVA, which blocks P/Q‐type Ca2+ channels. It peaked in 148 ms, had well‐defined kinetics and, unlike the sEPSC, was abolished by the phospholipase C (PLC) inhibitor U73122. It was blocked by the BK Ca2+‐activated K+ channel blocker iberiotoxin and unaffected by apamin, indicating selective activation of BK channels by PLC‐dependent store‐released Ca2+. The K+ conductance and underlying transient Ca2+ release showed a highly reproducible delay of 99.5 ms following PF burst stimulation, with a precision of 1–2 ms in repeated responses of the same PN, and a subsequent fast rise and fall of Ca2+ concentration. Analysis of Ca2+ signals showed that activation of the K+ conductance by Ca2+ release occured in small dendrites and subresolution structures, most probably spines. The results show that PF burst stimulation activates two pathways of mGluR1 signalling in PNs. First, transient, PLC‐dependent Ca2+ release from stores with precisely reproducible timing and second, slower Ca2+ influx in the cation‐permeable sEPSC channel. The priming by prior Ca2+ influx in P/Q‐type Ca2+ channels may determine the path of mGluR1 signalling. The precise timing of PLC‐mediated store release may be important for interactions of PF mGluR1 signalling with other inputs to the PN.
Response linearity in primary auditory cortex of the ferret
Authors: Ahmed Bashir , Garcia‐Lazaro Jose A. , Schnupp Jan W. H.
Published: February 2006

The responses of neurons within the primary auditory cortex (A1) of the ferret elicited by broadband dynamic spectral ripple stimuli were examined over a range of ripple spectral densities and ripple velocities. The large majority of neurons showed modulated responses to these stimuli and responded most strongly at low ripple densities and velocities. The period histograms of their responses were subjected to Fourier analysis, and the ratio of the magnitudes of the f1 and f0 (DC) components of these responses were calculated to give a quantitative index of response linearity. For 82 out of 396 neurons tested (20.7%) this ratio remained above 1.0 over the entire range of ripple densities and velocities. These neurons were classified as ‘consistently linear’. A further 134/396 (33.8%) of neurons maintained an f1/f0 ratio above 1.0 for either a range of ripple densities at a fixed ripple velocity, or over a range of ripple velocities at a specific ripple density, and were classified as ‘locally linear’. Interestingly, for the superficial layers of the primary auditory cortex, consistently linear and locally linear neurons outnumbered nonlinear neurons by a 2:1 ratio. The converse was true for the deep layers. Unlike in primary visual cortex, where f1/f0 ratios have been reported to exhibit a bimodal distribution with a minimum at f1/f0≈ 1, f1/f0 ratios for A1 are unimodally distributed with a peak at f1/f0≈ 1.
Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways
Authors: Bäumer Tobias , Bock Franka , Koch Giacomo , Lange Rüdiger , Rothwell John C. , Siebner Hartwig R. , Münchau Alexander
Published: February 2006

We explored interhemispheric facilitation (IHF) between (a) left and right primary motor cortex (M1) and (b) left dorsal premotor (dPM) and right M1 in 20 right‐handed healthy human subjects using a paired pulse transcranial magnetic stimulation (TMS) protocol. A conditioning TMS pulse (CP) applied to left M1 or dPM with an intensity of 80% and 60% active motor threshold (CP80%AMT and CP60%AMT, respectively) was followed by a test pulse (TP) over right M1 induced by anterior–posterior‐ or posterior–anterior‐ (TPAP, TPPA) directed currents in the brain at interstimulus intervals (ISIs) of 3–8 and 10 ms. EMG was recorded from left first dorsal interosseous muscle. In the main experimental condition IHF was evoked by CP80%AMT over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP80%AMT produced IHF at an ISI of 8 ms when applied over left dPM but only with TPPA. In addition, when CP60%AMT was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TPPA, indicating that IHF elicited over dPM was not caused by current spread of the conditioning pulse to M1. We conclude that IHF can be induced differentially by conditioning M1 and dPM using subthreshold CP. These facilitatory interactions depended on the intensity and ISI of the CP as well as the current flow direction of the TP. We suggest that not only do the CPs activate separate anatomical pathways but also that these pathways project to different populations of interneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.
ATP splitting by half the cross‐bridges can explain the twitch energetics of mouse papillary muscle
Authors: Widén C. , Barclay C. J.
Published: February 2006

The aim of this study was to quantify the fraction of cross‐bridges that cycle during a cardiac twitch. Measurements of the energetics of contracting left ventricular mouse papillary muscle were made in vitro (27°C) using the myothermic technique. Enthalpy output was partitioned into force‐dependent and force‐independent components using 2,3‐butanedione monoxime (BDM) to selectively inhibit cross‐bridge cycling. For isometric contractions and a contraction frequency of 2 Hz the net enthalpy output was 5.7 ± 0.8 mJ g−1 twitch−1 and initial enthalpy output was 2.3 ± 0.3 mJ g−1 twitch−1 (n= 11). Assuming that low concentrations of BDM did not affect Ca2+ cycling, force‐independent enthalpy output was 18.6 ± 1.9% (n= 7) of the initial enthalpy output. Enthalpy output decreased with increased contraction frequency but was independent of shortening velocity. On the basis of these values, it was calculated that the twitch energetics were consistent with ATP splitting by half the cross‐bridges and the pumping of one Ca2+ into the sarcoplasmic reticulum for every three cross‐bridge cycles. The simplest interpretation is that half the cross‐bridges completed one ATP‐splitting cycle in each twitch. The lack of influence of shortening velocity on energy cost supports the idea that the amount of energy to be used is determined early in a twitch and is not greatly influenced by events that occur during the contraction.
Modulation of Ca2+‐activated K+ currents and Ca2+‐dependent action potentials by exocytosis in goldfish bipolar cell terminals
Authors: Palmer Mary J.
Published: February 2006

Retinal bipolar cells convey light‐evoked potentials from photoreceptors to ganglion cells and mediate the initial stages of visual signal processing. They do not fire Na+‐dependent action potentials (APs) but the Mb1 class of goldfish bipolar cell exhibits Ca2+‐dependent APs and regenerative potentials that originate in the axon terminal. I have examined the properties of Ca2+‐dependent APs in isolated bipolar‐cell terminals in goldfish retinal slices. All recorded terminals fired spontaneous or evoked APs at frequencies of up to 15 Hz. When an AP waveform was used as a voltage stimulus, exocytosis was evoked by single APs, maintained throughout AP trains and modulated by AP frequency. Furthermore, feedback inhibition of the Ca2+ current (ICa) by released vesicular protons reduced depression of exocytosis during AP trains. In the absence of K+ current inhibition, step depolarizations and AP waveforms evoked a rapidly activated outward current that was dependent on Ca2+ influx (IK(Ca)). I therefore investigated whether proton‐mediated feedback inhibition of ICa affected the activation of IK(Ca). A transient inhibition of IK(Ca) was observed that was dependent on exocytosis, blocked by high‐pH extracellular buffer, of similar magnitude to inhibition of ICa but occurred with a delay of 2.7 ms. In addition, the amplitude of APs evoked under current clamp was inhibited by the action of vesicular protons released by the APs. Protons released via exocytosis may therefore be a significant modulator of Ca2+‐dependent currents and regenerative potentials in bipolar‐cell terminals.
Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Authors: Liu Philip T. , Stenger Steffen , Li Huiying , Wenzel Linda , Tan Belinda H. , Krutzik Stephan R. , Ochoa Maria Teresa , Schauber Jürgen , Wu Kent , Meinken Christoph , Kamen Diane L. , Wagner Manfred , Bals Robert , Steinmeyer Andreas , Zügel Ulrich , Gallo Richard L. , Eisenberg David , Hewison Martin , Hollis Bruce W. , Adams John S. , Bloom Barry R. , Modlin Robert L.
Published: February 2006

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1–hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular
Mycobacterium tuberculosis
. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D–mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
A Periodically Active Pulsar Giving Insight into Magnetospheric Physics
Authors: Kramer M. , Lyne A. G. , O'Brien J. T. , Jordan C. A. , Lorimer D. R.
Published: February 2006

PSR B1931+24 (J1933+2421) behaves as an ordinary isolated radio pulsar during active phases that are 5 to 10 days long. However, when the radio emission ceases, it switches off in less than 10 seconds and remains undetectable for the next 25 to 35 days, then switches on again. This pattern repeats quasi-periodically. The origin of this behavior is unclear. Even more remarkably, the pulsar rotation slows down 50% faster when it is on than when it is off. This indicates a massive increase in magnetospheric currents when the pulsar switches on, proving that pulsar wind plays a substantial role in pulsar spin-down. This allows us, for the first time, to estimate the magnetospheric currents in a pulsar magnetosphere during the occurrence of radio emission.