bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of bone microanatomy of the tetrapod tibia and its use in palaeobiological inference
Authors: KRILOFF A. , GERMAIN D. , CANOVILLE A. , VINCENT P. , SACHE M. , LAURIN M.
Published: February 2008

Bone microanatomy appears to track changes in various physiological or ecological properties of the individual or the taxon. Analyses of sections of the tibia of 99 taxa show a highly significant (P ≤ 0.005) relationship between long‐bone microanatomy and habitat. Randomization tests reveal a highly significant (P ≤ 0.005) phylogenetic signal on several compactness profile parameters and lifestyle. Discriminant analyses yield an inference model which has a success rate of 63% when lifestyle is coded into three states (aquatic, amphibious and terrestrial) or 83% for a binary model (aquatic vs. amphibious to terrestrial). Lifestyle is inferred to have been terrestrial for the stem‐tetrapodDiscosauriscus(Early Permian), the basal synapsidDimetrodon(Early Permian), the dicynodont therapsidDicynodon(Late Permian), an unindentified gorgonopsian (Late Permian); the parareptilePareiasaurus(Middle or Late Permian) is modelled as being aquatic, but was more likely amphibious.
Marine reserves: size and age do matter
Authors: Claudet Joachim , Osenberg Craig W. , Benedetti‐Cecchi Lisandro , Domenici Paolo , García‐Charton José‐Antonio , Pérez‐Ruzafa Ángel , Badalamenti Fabio , Bayle‐Sempere Just , Brito Alberto , Bulleri Fabio , Culioli Jean‐Michel , Dimech Mark , Falcón Jesús M. , Guala Ivan , Milazzo Marco , Sánchez‐Meca Julio , Somerfield Paul J. , Stobart Ben , Vandeperre Frédéric , Valle Carlos , Planes Serge
Published: February 2008

Marine reserves are widely used throughout the world to prevent overfishing and conserve biodiversity, but uncertainties remain about their optimal design. The effects of marine reserves are heterogeneous. Despite theoretical findings, empirical studies have previously found no effect of size on the effectiveness of marine reserves in protecting commercial fish stocks. Using 58 datasets from 19 European marine reserves, we show that reserve size and age do matter: Increasing the size of the no‐take zone increases the density of commercial fishes within the reserve compared with outside; whereas the size of the buffer zone has the opposite effect. Moreover, positive effects of marine reserve on commercial fish species and species richness are linked to the time elapsed since the establishment of the protection scheme. The reserve size‐dependency of the response to protection has strong implications for the spatial management of coastal areas because marine reserves are used for spatial zoning.
Site‐specific microbial communities in three PCB‐impacted sediments are associated with different in situ dechlorinating activities
Authors: Kjellerup Birthe V. , Sun Xueli , Ghosh Upal , May Harold D. , Sowers Kevin R.
Published: February 2008

Competitive PCR and denaturing HPLC analyses together with an assay detecting potential polychlorinated biphenyl (PCB) dechlorinating activities were combined with physical‐chemical site characterizations to identify factors affecting the reductive dechlorination of PCBs in the three historically impacted sediments: Grasse and Buffalo Rivers, NY and Anacostia River, DC. In Grasse River sediment an in situ enriched population of Dehalococcoides phylotypes was abundant in high numbers together with a relatively high dechlorination activity and a high concentration of congeners containing unflanked chlorine substitutions. In contrast microbial communities in Anacostia and Buffalo Rivers sediments consisted of similar total numbers of putative dechlorinating bacteria, but the populations consisted of more diverse putative dechlorinating phylotypes and were associated with lower dechlorination activities and higher concentrations of flanked congeners. Differences observed in the PCB dechlorination activity were not influenced by the chemical PCB availability in spiked sediment or physical sediment characteristics, but were consistent with the concentration of PCBs and total organic carbon in the native sediment. Application of molecular methods for selective detection of indigenous microbial dechlorinating communities combined with assessment of the dechlorinating activity and analysis of the in situ congener profiles provided a comprehensive approach for characterization and identification of sites that are amenable to bioremediation, which is essential for the development of in situ treatment strategies.
Transcription and activities of NOx reductases in Agrobacterium tumefaciens: the influence of nitrate, nitrite and oxygen availability
Authors: Bergaust Linda , Shapleigh James , Frostegård Åsa , Bakken Lars
Published: February 2008

The ability of Agrobacetrium tumefaciens to perform balanced transitions from aerobic to anaerobic respiration was studied by monitoring oxygen depletion, transcription of nirK and norB, and the concentrations of nitrite, nitric oxide (NO) and nitrous oxide in stirred batch cultures with different initial oxygen, nitrate or nitrite concentrations. Nitrate concentrations (0.2–2 mM) did not affect oxygen depletion, nor the oxygen concentration at which denitrification was initiated (1–2 μM). Nitrite (0.2–2 mM), on the other hand, retarded the oxygen depletion as it reached ≈20 μM, and caused initiation of active denitrification as oxygen concentrations reached 10–17 μM. Unbalanced transitions occurred in treatments with high cell densities (i.e. with rapid transition from oxic to anoxic conditions), seen as NO accumulation to μM concentrations and impeded nitrous oxide production. This phenomenon was most severe in nitrite treatments, and reduced the cells' ability to respire oxygen during subsequent oxic conditions. Transcripts of norB were only detectable during the period with active denitrification. In contrast, nirK transcripts were detected at low levels both before and after this period. The results demonstrate that the transition from aerobic to anaerobic metabolism is a regulatory challenge, with implications for survival and emission of trace gases from denitrifying bacteria.
Isolation and cultivation of canine corneal cells for in vitro studies on the anti‐inflammatory effects of dexamethasone
Authors: Werner Anke , Braun Michael , Kietzmann Manfred
Published: February 2008

Objective  This study was conducted to establish a protocol for the isolation and culture of canine corneal cells (i.e. endothelium, keratocytes, and epithelium) to be used for in vitro studies on the effects of dexamethasone in corneal inflammation.

Animal material  Corneal endothelial cells, epithelial cells and keratocytes from enucleated eyes of dogs (euthanized not related to this study) were isolated and cultured.

Procedure  Canine corneal cells were isolated using a combined enzymatic and mechanical technique and separately taken into culture. The three different cell types were verified by phase contrast microscopy, immunofluorescence, and Western blot using antivimentin and anticytokeratin antibodies. The mRNA for the glucocorticoid receptor (GR) was detected using reverse transcriptase polymerase chain reaction (RT‐PCR).

To study dexamethasone effects, primary cells were stimulated with lipopolysaccharides (LPS) to induce production of inflammatory mediators, particularly prostaglandin E2 (PGE2). The concentration of PGE2 in cell culture supernatant was determined utilizing an ELISA assay. Results were compared between control, stimulated as well as stimulated and dexamethasone treated cells.

Results  A protocol for the isolation and culture of canine corneal endothelium, keratocytes, and epithelium was successfully established. Using morphological criteria as well as immunocytochemistry and Western blotting the identity of the cells could be verified. RT‐PCR of the primary cells showed mRNA for the GR in all three cell types of the canine cornea. Furthermore, stimulation with LPS led to an increased PGE2‐production in epithelial cells and fibroblasts, which was significant for epithelial cells. The PGE2‐concentration was decreased in a dose dependent manner by the addition of dexamethasone.

Conclusion  The three major cell types of the canine cornea (i.e. endothelium, keratocytes, and epithelium) can be isolated and cultured in vitro. The mRNA for the GR is shown in all three cell types, its functionality is demonstrated by the dose dependent reduction of PGE2‐production following dexamethasone treatment.
Congenital orbital cysts of neural tissue in two dogs
Authors: Regnier Alain , Raymond‐Letron Isabelle , Peiffer Robert L.
Published: February 2008

A 3‐month‐old English Cocker Spaniel and a 6‐month‐old miniature poodle presented with clinical signs related to an abnormal right eye since birth. In both dogs, the right globe could not be identified and was replaced by a fluctuant intraorbital mass covered by a vascularized mucous membrane. Ultrasonography demonstrated that both masses were cystic structures markedly larger in size than the normal contralateral globes. In both cases, surgical excision revealed a multilobular cyst filling the whole orbital cavity. Histopathologic examination and immunostaining for glial fibrillary acid protein and S100 protein supported a diagnosis of neural cysts associated with ocular dysplasia. The definitive diagnosis was congenital cystic eye and microphthalmos with cyst for the Cocker Spaniel and miniature poodle, respectively. Karyotype was normal in both dogs. Congenital cystic eye and microphthalmos with cyst result from defects in early embryonic life that arise following formation of the optic vesicle and prior to closure of the optic fissure. To the authors’ knowledge neither has been reported in the canine species. They should be considered in the differential diagnosis of orbital cysts in dogs.
Isolation of obligate anaerobic bacteria from ulcerative keratitis in domestic animals
Authors: Ledbetter Eric C. , Scarlett Janet M.
Published: February 2008

Objective To determine the frequency of obligate anaerobic bacterial isolation from corneal samples of domestic animals with ulcerative keratitis and to characterize the historical, clinical, cytological, and microbiological features of culture‐positive cases.

Animals studied Three hundred and thirty domestic animals with ulcerative keratitis.

Procedures Anaerobic bacteriologic culture and Gram stain were performed on corneal samples from consecutive animals examined with suspect septic ulcerative keratitis. Additional corneal diagnostics included: aerobic bacteriologic culture for all species; fungal culture for ungulates;Mycoplasmaculture and virus isolation or feline herpesvirus‐1 (FHV‐1) polymerase chain reaction (PCR) for cats. Historical, clinical, and cytological findings were correlated with microbiologic data.

Results Anaerobic bacteria were isolated from 13.0% of corneal samples (dogs: 14.0%; horses: 12.9%; cats: 7.9%; alpacas: 18.8%). The most frequent isolates wereClostridium,Peptostreptococcus,Actinomyces,Fusobacterium, andBacteroidesspecies. The majority of these infections were mixed anaerobic and aerobic bacteria, unless antimicrobial therapy had been administered prior to presentation. The clinical appearance of anaerobic bacterial culture‐positive cases was highly variable. Ocular trauma, pre‐existing corneal disease, previous corneal surgery, and chronic dermatological disease were significantly (P ≤ 0.05) correlated with positive anaerobic cultures in one or more species.

Conclusions The results of the present study demonstrate that obligate anaerobic bacteria are present within the intralesional flora of ulcerative keratitis in domestic animals. In most species evaluated, these bacteria were identified infrequently. Anaerobic bacterial infection of the cornea most frequently occurs in association with other ocular pathogens and previous corneal abnormalities.
ON THE CONVERGENCE OF EMPIRICAL PROCESSES OF MIXING VARIABLES1
Authors: Wuhees C. S.
Published: February 2008

Conditions are given for the weak convergence of (t—t2)LN(aN‐1(t)) to a Gaussian process where v<1/2, aN is a cdf and LN is the normalized weighted empirical cumulative distribution function (cdf) for an α‐mixing sample of random variables in R which may be non‐stationary with discontinuous marginals.
A NOTE ON OPTIMUM STRATIFICATION FOR EQUAL ALLOCATION WITH RATIO AND REGRESSION METHODS OF ESTIMATION
Authors: Singh Ravindra
Published: February 2008

When the information on a highly positively correlated auxiliary variable x is used to construct stratified regression (or ratio) estimates of the population mean of the study variable y, the paper considers the problem of determining approximately optimum strata boundaries (AOSB) on x when the sample size in each stratum is equal. The form of the conditional variance function V(y/x) is assumed to be known. A numerical investigation into the relative efficiency of equal allocation with respect to the Neyman and proportional allocations has also been made. The relative efficiency of equal allocation with respect to Neyman allocation is found to be nearly equal to one.
One‐Sample Probability Plots
Authors: Fisher N. I.
Published: February 2008

A graphical procedure based on the sample distribution function is shown to be useful for assessing the symmetry of the underlying population, both from a descriptive and a computational point of view. To some extent, it complements graphical techniques based on the sample quantiles.
ESTIMATING THE MAXIMUM (MINIMUM) OF A QUADRATIC FUNCTION UNDER CERTAIN CORRELATION PATTERNS
Authors: Scariano Stephen M.
Published: February 2008

May nonidentity error correlation patterns encountered in regression theory allow computationally efficient techniques for modifying the usual procedures for constructing confidence intervals and performing F‐tests so that valid inferences can be drawn. Such techniques are explored in light of the general theme of this note.
CORRELATIONS AND CHARACTERIZATIONS OF THE UNIFORM DISTRIBUTION
Authors: Brown Timothy C. , Cartwright Donald I. , Eagleson G. K.
Published: February 2008

Two characterizations of the uniform distribution on a suitable compact space are proved. These characterizations are applied to a number of particular examples of which the most interesting is the following: if X, Y and Z are independent n‐vectors whose components are independent and identically distributed within a vector, then the pairwise independence of the product moment correlation coefficients between X, Y and Z implies that these vectors are normally distributed.
ROBUST COMPARISON OF DISPERSIONS FOR SAMPLES OF DIRECTIONAL DATA
Authors: Fisher N. I.
Published: February 2008

Robust methods are proposed for testing whether several directional distributions on the unit p‐sphere have comparable dispersions. The families of distributions considered are the Langevin for random vectors, and the Generalised Scheidegger‐Watson for random axes, with specific interest in the Fisher and Watson distributions on the sphere. The methods are analogues of Levene's procedure for comparing variances of normal distributions.
DEGREE, ITERATION AND PERMUTATION IN IMPROVING BONFERRONI‐TYPE BOUNDS
Authors: Seneta E.
Published: February 2008

summary

This note has as its starting points: 1) the upper bound of Worsley (1982) for the probability of union of n events: 2) the iterative procedure of Hoppe (1985) for deriving successive upper and lower Bonferroni‐type bounds, in alternation, for the probability of such a union. We first show that Worsley's bound (and hence successive bounds based on it) can be sharpened by an initial application of 2) to an appropriate lower bound due to Boole (1854). Subsequently, we show that if the n events are exchangeable, the sequence of bounds obtained from this starting point is that due to Sobel and Uppuluri (1972). The role of degree of a bound is explored, as well as sharpening of bounds by permutation when events are not necessarily exchangeable.
BAYESIAN ANALYSIS OF THE LINEAR REGRESSION MODEL WITH NON‐NORMAL DISTURBANCES
Authors: Chaturvedi Anoop , Hasegawa Hikaru , Asthana Sheel
Published: February 2008

This paper considers the Bayesian analysis of a linear regression model with identically independently distributed non‐normal disturbances. The distribution of disturbances is approximated by an Edgeworth series distribution with cumulants, of order higher than fourth, negligible. The posterior distribution of the regression coefficients vector is obtained under the assumption of a g‐prior distribution for the parameters of the model. The Bayes estimator and its Bayes risk of the estimator are derived under a quadratic loss structure.
RIGHTS, INDIRECT HARMS AND THE NON‐IDENTITY PROBLEM
Authors: MCBRAYER JUSTIN PATRICK
Published: February 2008

The non‐identity problem is the problem of grounding moral wrongdoing in cases in which an action affects who will exist in the future. Consider a woman who intentionally conceives while on medication that is harmful for a fetus. If the resulting child is disabled as a result of the medication, what makes the woman's action morally wrong? I argue that an explanation in terms of harmful rights violations fails, and I focus on Peter Markie's recent rights‐based defense. Markie's analysis rests on the notion of an indirect harm, and I show that the calculation of an indirect harm relies on an improper baseline for the determination of whether or not an action adversely affects a patient's interests. I also defend an impersonal duty‐based analysis of the wrongdoing in non‐identity cases against an objection by Markie. I close by arguing that the rights‐based analysis is insensitive to context and that context is morally relevant in the determination of the moral valence of actions in cases of non‐identity. This failure provides a pro tanto reason to favor an impersonal duty‐based analysis of the wrongdoing in non‐identity cases.
MORAL QUALMS, FUTURE PERSONS, AND EMBRYO RESEARCH
Authors: SHAW DAVID MARTIN
Published: February 2008

Many people have moral qualms about embryo research, feeling that embryos must deserve some kind of protection, if not so much as is afforded to persons. This paper will show that these qualms serve to camouflage motives that are really prudential, at the cost of also obscuring the real ethical issues at play in the debate concerning embryo research and therapeutic cloning. This in turn leads to fallacious use of the Actions/Omissions Distinction and ultimately neglects the duties that we have towards future persons.
Inflation and Unemployment in General Equilibrium*
Authors: Rocheteau Guillaume , Rupert Peter , Wright Randall
Published: February 2008

When labor is indivisible, there exist efficient outcomes with some agents randomly unemployed, as in Rogerson (1988). We integrate this idea into the modern theory of monetary exchange, where some trade occurs in centralized markets and some in decentralized markets, as in Lagos and Wright (2005). This delivers a general equilibrium model of unemployment and money, with explicit microeconomic foundations. We show that the implied relation between inflation and unemployment can be positive or negative, depending on simple preference conditions. Our Phillips curve provides a long‐run, exploitable, trade‐off for monetary policy; it turns out, however, that the optimal policy is the Friedman rule.
Heterogeneity, Job Creation and Unemployment Volatility
Authors: Guerrieri Veronica
Published: February 2008

In this paper, I explore the impact of match‐specific heterogeneity at the job creation margin on business cycle fluctuations. I show that this form of heterogeneity alone does not help to amplify labor market volatility, either under full or under asymmetric information. First, I show analytically that, under full information, heterogeneity has no first‐order effect on the response of unemployment and job creation to productivity, and actually tends to dampen the response of market tightness. Then, in a series of calibrations, I show that with both full and asymmetric information, the model delivers labor market volatilities close to the representative‐agent, full‐information benchmark.
Testing and the Composition of the Labor Pool
Authors: Boone Johnathan , Watson Joel
Published: February 2008

We consider a continuous‐time labor matching model with endogenous separation. Firms initially lack information about the quality of workers with whom they are matched. They acquire information both from pre‐employment testing and, in the case in which a labor relationship is established, on‐the‐job performance. Testing provides a signal of a worker's quality. A firm can pick the accuracy level of its test, but it pays a cost that increases in the accuracy. Workers who perform poorly on the test are not offered employment; those who perform poorly on the job are eventually fired (after some delay). Worker quality is not match‐specific; low‐quality workers are less productive with all firms. We show that, in equilibrium, there is an inverse and complementary relation between the level of testing that firms optimally perform and the overall quality of the workers in the matching pool. We consider the properties of a steady‐state, stable equilibrium in such an environment. The complementarity between testing and the composition of the unemployed pool introduces the possibility of multiple equilibria.
PROFIT, SURPLUS PRODUCT, EXPLOITATION AND LESS THAN MAXIMIZED UTILITY: A NEW EQUIVALENCE PROPOSITION ON THE FUNDAMENTAL MARXIAN THEOREM
Authors: Matsuo Tadasu
Published: February 2008

Morishima's Generalized Fundamental Marxian Theorem (GFMT) is an extended form of Okishio's Fundamental Marxian Theorem, which showed the equivalence between positive profit and the exploitation of labor. GFMT is not developed as a system of equivalence proposition between five conditions, which I call ‘The Strong System of Exploitation Theory’. But by the definition of this system, there remains the possibility of positive profit without exploitation. In this paper, I demonstrated an alternative system of equivalence proposition, naming it ‘The Weak System of Exploitation Theory’, in which positive profits always mean exploitation. Here I introduced workers' utility function to define the exploitation concept. Then I could also show that the exploitation is equivalent with the situation where workers' utilities are under‐maximized.
THEORETICAL FOUNDATIONS OF PAY‐AS‐YOU‐GO DEFINED‐CONTRIBUTION PENSION SCHEMES
Authors: Gronchi Sandro , Nisticò Sergio
Published: February 2008

The paper inquires into notional defined contribution pension schemes, which retain the pay‐as‐you‐go financing method while adopting the award and indexation formulas typical of funded, defined‐contribution systems. It examines the properties of the new arrangement and compares them with those of the traditional defined‐benefit pay‐as‐you‐go schemes.
MICRO EMPIRICAL RESULTS OF A KALECKIAN‐TYPE CAPITAL ACCUMULATION MODEL COMPARED WITH MACRO RESULTS FOR SOME EUROPEAN ECONOMIES
Authors: Gander James P.
Published: February 2008

A micro economic model of the rate of capital accumulation that corresponds to a macro Kaleckian‐type post‐Keynesian investment function is hypothesized. Firm‐level accounting data on industrial and commercial firms over the time period 1994–2000 for three European economies and the USA are used to test the consistency of the micro model with the macro model of Hein and Ochsen (2003, Metroeconomica, 54, pp. 404–33). The micro empirical results were very consistent with the macro results, suggesting a strong micro foundation to the macro investment function. In addition country differences and industry differences were included in the analysis.
A Bootstrap Method for Identifying and Evaluating a Structural Vector Autoregression*
Authors: Demiralp Selva , Hoover Kevin D. , Perez Stephen J.
Published: February 2008

Graph‐theoretic methods of causal search based on the ideas of Pearl (2000), Spirtes et al. (2000), and others have been applied by a number of researchers to economic data, particularly by Swanson and Granger (1997) to the problem of finding a data‐based contemporaneous causal order for the structural vector autoregression, rather than, as is typically done, assuming a weakly justified Choleski order. Demiralp and Hoover (2003) provided Monte Carlo evidence that such methods were effective, provided that signal strengths were sufficiently high. Unfortunately, in applications to actual data, such Monte Carlo simulations are of limited value, as the causal structure of the true data‐generating process is necessarily unknown. In this paper, we present a bootstrap procedure that can be applied to actual data (i.e. without knowledge of the true causal structure). We show with an applied example and a simulation study that the procedure is an effective tool for assessing our confidence in causal orders identified by graph‐theoretic search algorithms.
Strategic Arts‐Based Peacebuilding
Authors: Shank Michael , Schirch Lisa
Published: February 2008

The arts offer peacebuilders unique tools for transforming intractable interpersonal, intercommunal, national, and global conflicts—tools that are not currently prevalent or available within the peacebuilding field. The task for peacebuilding practitioners is to find strategic ways of incorporating the arts into the work of peacebuilding and to create a space where people in conflict can express themselves, heal themselves, and reconcile themselves through the arts. There is very little solid theory, research, or evaluation of arts‐based peacebuilding. This article seeks to move beyond a simplistic approach that asserts the “arts are powerful” to a richer articulation of how they function in peacebuilding, when to use them, what they can do, and how to evaluate their usage. This article provides examples of and the conceptual frameworks behind strategic arts‐based peacebuilding.
Was Einstein Really a Pacifist? Einstein's Forward‐Thinking, Pragmatic, Persistent Pacifism1
Authors: Holmes Virginia Iris
Published: February 2008

This article examines Einstein's pacifist convictions, as revealed by public and private statements throughout his life, with particular attention to two periods when his identity as a pacifist might be most challenged: (a) the start of the Nazi regime in Germany in 1933, when he continued to claim a pacifist identity but argued that refusal of military service was no longer appropriate or effective in current circumstances; and (b) the aftermath of the dropping of two atomic bombs on Japan in August 1945, when critics, including some Japanese, pointed to his early groundbreaking work in physics as having made the bomb possible and his efforts in 1939 to urge the United States government to produce such a bomb before Germany. The author argues that Einstein maintained a constant pacifist identity throughout his life, interweaving it with a commitment to social justice, insightful concerns about the relationship between Jews and Arabs in Palestine, and a core belief in supranational world government as the truly effective avenue to ending war. Although his sense of pacifism evolved significantly in response to historical developments, he thoughtfully and clearly articulated his reasoning behind these shifts.
Acute partial transverse myelitis: risk factors for conversion to multiple sclerosis
Authors: Sellner J. , Lüthi N. , Bühler R. , Gebhardt A. , Findling O. , Greeve I. , Mattle H. P.
Published: February 2008

Acute partial transverse myelitis (APTM) may be the first clinical manifestation of multiple sclerosis (MS), of relapsing myelitis, or remain a monophasic event. Identification of risk factors associated with relapse or conversion to MS is important, as prognostic information might help to guide management. The objective of this study was to define clinical, laboratory and neuroimaging factors in patients with first‐ever APTM that predict relapses or conversion to MS. We identified 73 patients with a first‐ever APTM admitted to our institution from January 1999 to June 2005. The follow‐up time ranged from 12 to 90 months (mean follow‐up 46 months). Patient demographics, clinical impairment at onset and after 3 months, ancillary tests including cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), evoked potentials, recurrent and new symptoms and signs during follow‐up were analysed. APTM remained a monophasic event in 35 patients (47.9%), conversion to MS occurred in 32 (43.8%) and recurred as relapsing myelitis in six patients (8.2%). According to univariate analysis, a family history of MS (P = 0.02), higher expanded disability status scale (EDSS) at onset (P = 0.03) and lesions on brain MRI (P = 0.03) were predictive factors for conversion to MS. CSF‐specific oligoclonal bands (P = 0.04) or abnormal IgG‐index (P = 0.04) were associated with increased risk for MS as well. In patients with a first‐ever APTM, a family history of MS, high EDSS at presentation, lesions on brain MRI, CSF‐specific oligoclonal bands or abnormal IgG‐index may indicate an increased risk for conversion to MS.
Informationist programme in support of biomedical research: a programme description and preliminary findings of an evaluation
Authors: Whitmore Susan C. , Grefsheim Suzanne F. , Rankin Jocelyn A.
Published: February 2008

Background:  The informationist programme at the Library of the National Institutes of Health (NIH) in Bethesda, MD, USA has grown to 14 informationists working with 40 clinical and basic science research teams.

Purpose:  This case report, intended to contribute to the literature on informationist programmes, describes the NIH informationist programme, including implementation experiences, the informationists’ training programme, their job responsibilities and programme outcomes.

Brief description:  The NIH informationist programme was designed to enhance the library's service capacity. Over time, the steps for introducing the service to new groups were formalized to ensure support by leadership, the team being served and the library. Job responsibilities also evolved from traditional library roles to a wide range of knowledge management activities. The commitment by the informationist, the team and the library to continuous learning is critical to the programme's success.

Results / outcomes:  NIH scientists reported that informationists saved them time and contributed to teamwork with expert searching and point‐of‐need instruction. Process evaluation helped refine the programme.

Evaluation method:  High‐level, preliminary outcomes were identified from a survey of scientists receiving informationist services, along with key informant interviews. Process evaluation examined service implementation, informationists’ training and service components. Anecdotal evidence has also indicated a favourable response to the programme.
Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model
Authors: Wollack Jan B. , Makori Benedette , Ahlawat Stuti , Koneru Rajeth , Picinich Sonia C. , Smith Angela , Goldman I. David , Qiu Andong , Cole Peter D. , Glod John , Kamen Barton
Published: February 2008

J. Neurochem. (2008) 104, 1494–1503.

Reduced derivatives of folic acid (folates) play a critical role in the development, function and repair of the CNS. However, the molecular systems regulating folate uptake and homeostasis in the central nervous system remain incompletely defined. Choroid plexus epithelial cells express high levels of folate receptor α (FRα) suggesting that the choroid plays an important role in CNS folate trafficking and maintenance of CSF folate levels. We have characterized 5‐methyltetrahydrofolate (5‐MTHF) uptake and metabolism by primary rat choroid plexus epithelial cells in vitro. Two distinct processes are apparent; one that is FRα dependent and one that is independent of the receptor. FRα binds 5‐MTHF with high affinity and facilitates efficient uptake of 5‐MTHF at low extracellular folate concentrations; a lower affinity FRα independent system accounts for increased folate uptake at higher concentrations. Cellular metabolism of 5‐MTHF depends on the route of folate entry into the cell. 5‐MTHF taken up via a non‐FRα ‐mediated process is rapidly metabolized to folylpolyglutamates, whereas 5‐MTHF that accumulates via FRα remains non‐metabolized, supporting the hypothesis that FRα may be part of a pathway for transcellular movement of the vitamin. The proton‐coupled folate transporter, proton‐coupled folate transporter (PCFT), mRNA was also shown to be expressed in choroid plexus epithelial cells. This is consistent with the role we have proposed for proton‐coupled folate transporter in FRα‐mediated transport as the mechanism of export of folates from the endocytic compartment containing FRα.
Altered expression and subcellular distribution of GRK subtypes in the dopamine‐depleted rat basal ganglia is not normalized byl‐DOPA treatment
Authors: Ahmed M. Rafiuddin , Bychkov Evgeny , Gurevich Vsevolod V. , Benovic Jeffrey L. , Gurevich Eugenia V.
Published: February 2008

J. Neurochem. (2008)104,1622–1636.

Dysregulation of dopamine (DA) receptors is believed to underlie Parkinson’s disease pathology andl‐DOPA‐induced motor complications. DA receptors are subject to regulation by G protein‐coupled receptor kinases (GRKs) and arrestins. DA lesion with 6‐hydroxydopamine caused multiple protein‐ and brain region‐specific changes in the expression of GRKs. In the globus pallidus, all four GRK isoforms (GRK2, 3, 5, 6) were reduced in the lesioned hemisphere. In the caudal caudate‐putamen (cCPu) three GRK isoforms (GRK2, 3, 6) were decreased by DA depletion. The decrease in GRK proteins in globus pallidus, but not cCPu, was mirrored by reduction in mRNA. GRK3 protein was reduced in the rostral caudate‐putamen (rCPu), whereas other isoforms were either unchanged or up‐regulated. GRK6 protein and mRNA were up‐regulated in rCPu and nucleus accumbens.l‐DOPA (25 mg/kg, twice daily for 10 days) failed to reverse changes caused by DA depletion, whereas D2/D3agonist pergolide (0.25 mg/kg daily for 10 days) restored normal levels of expression of GRK5 and 6. In rCPu, GRK2 protein was increased in most subcellular fractions byl‐DOPA but not by DA depletion alone. Similarly,l‐DOPA up‐regulated arrestin3 in membrane fractions in both regions. GRK5 was down‐regulated byl‐DOPA in cCPu in the light membrane fraction, where this isoform is the most abundant. The data suggest that alterations in the expression and subcellular distribution of arrestins and GRKs contribute to pathophysiology of Parkinson’s disease. Thus, these proteins may be targets for antiparkinsonian therapy.
Curcumin binds to the α‐helical intermediate and to the amyloid form of prion protein – a new mechanism for the inhibition of PrPSc accumulation
Authors: Hafner‐Bratkovič Iva , Gašperšič Jernej , Šmid Lojze M. , Bresjanac Mara , Jerala Roman
Published: February 2008

J. Neurochem. (2008) 104, 1553–1564.

Conversion of the native, predominantly α‐helical conformation of prion protein (PrP) into the β‐stranded conformation is characteristic for the transmissible spongiform encephalopathies such as Creutzfeld–Jakob disease. Curcumin, an extended planar molecule and a dietary polyphenol, inhibits in vitro conversion of PrP and formation of protease resistant PrP in neuroblastoma cell lines. Curcumin recognizes the converted β‐form of the PrP both as oligomers and fibrils but not the native form. Curcumin binds to the prion fibrils in the left‐handed chiral arrangement as determined by circular dichroism. We show that curcumin labels the plaques of the brain sections of variant Creutzfeld–Jakob disease cases and stains the same structures as antibodies against the PrP. In contrast to thioflavin T, curcumin also binds to the α‐helical intermediate of PrP present at acidic pH at stoichiometry of 1 : 1. Congo red competes with curcumin for binding to the α‐intermediate as well as to the β‐form of PrP but is toxic and binds also to the native form of PrP. We therefore show that the partially unfolded structural intermediate of the PrP can be targeted by non‐toxic compound of natural origin.
Differential activation of the calcium/protein kinase C and the canonical β‐catenin pathway by Wnt1 and Wnt7a produces opposite effects on cell proliferation in PC12 cells
Authors: Spinsanti Paola , De Vita Teresa , Caruso Alessandra , Melchiorri Daniela , Misasi Roberta , Caricasole Andrea , Nicoletti Ferdinando
Published: February 2008

J. Neurochem. (2008) 104, 1588–1598.

We examined the effect of Wnt1 and Wnt7a on cell proliferation using undifferentiated PC12 cells, which originate from the neural crest and are widely employed as a neuronal cell model. Heterologous expression of Wnt1 enhanced [3H]thymidine incorporation and expression of cyclin D1 and cylin E in PC12 cells. Opposite effects were observed in PC12 cells expressing Wnt7a. Searching for the mechanisms underlying the opposite effects of Wnt1 and Wnt7a on PC12 cell proliferation, we examined the activation of the canonical β‐catenin/T‐cell–lymphoid enhancer‐binding protein transcription factor pathway and the ‘calcium pathway’ by co‐transfecting the cells with a reporter gene controlled by either T‐cell–lymphoid enhancer‐binding protein transcription factor or the calcium‐activated transcription factor, NFAT. Wnt1 and Wnt7a activated both pathways, but to a different extent. While Wnt1 preferentially activated the calcium pathway, Wnt7a mainly activated the canonical pathway. Pharmacological inhibition of protein kinase C, which is a component of the calcium pathway, abrogated the increase in cell proliferation induced by Wnt1 without affecting the antiproliferative action of Wnt7a. The action of Wnt7a was instead occluded by lithium ions, which mimic the activation of the canonical pathway, and was largely reduced by Dickkopf‐1, which acts as an inhibitor of the canonical pathway. In addition, expression of a constitutively active mutant of β‐catenin potently activated the canonical Wnt pathway and reduced [3H]thymidine incorporation. These data challenge the view that the canonical Wnt pathway invariably supports cell growth and suggest that, at least in PC12 cells, cell proliferation is regulated by the balance between the calcium/protein kinase C pathway and the canonical pathway.
Identification of poly‐ADP‐ribosylated mitochondrial proteins after traumatic brain injury
Authors: Lai Yichen , Chen Yaming , Watkins Simon C. , Nathaniel Paula D. , Guo Fengli , Kochanek Patrick M. , Jenkins Larry W. , Szabó Csaba , Clark Robert S. B.
Published: February 2008

J. Neurochem. (2008) 104, 1700–1711.

Poly‐ADP‐ribosylation is a post‐translational modification performed by poly(ADP‐ribose) polymerases (PARP), involved in many diverse cellular functions including DNA repair, transcription, and long‐term potentiation. Paradoxically, PARP over‐activation under pathologic conditions including traumatic brain injury (TBI) results in cell death. We previously demonstrated that intra‐mitochondrial poly‐ADP‐ribosylation occurs following excitotoxic and oxidative injury in vitro. Here we sought to identify mitochondrial proteins modified by poly‐ADP‐ribosylation after TBI in vivo. Poly‐ADP‐ribosylation within mitochondria from injured brain after experimental TBI in rats was first verified using western blot and immuno‐electron microscopy. Poly‐ADP‐ribosylated mitochondrial proteins identified using a targeted proteomic approach included voltage‐dependent anion channel‐1, mitofilin, mitochondrial stress proteins, and the electron transport chain components F1F0 ATPase, cytochrome c oxidase, and cytochrome c reductase. To examine the functional consequences of mitochondrial poly‐ADP‐ribosylation, isolated rat brain mitochondria were exposed to conditions of nitrosative stress known to activate PARP. PARP activation‐induced reductions in State 3 respiration were prevented by the PARP‐1 inhibitor 5‐iodo‐6‐amino‐1,2‐benzopyrone or exogenous poly(ADP‐ribose) glycohydrolase. As the effects of PARP activation on mitochondrial respiration appear regulated by poly(ADP‐ribose) glycohydrolase, a direct effect of poly‐ADP‐ribosylation on electron transport chain function is suggested. These findings may be of relevance to TBI and other diseases where mitochondrial dysfunction occurs.
6‐Hydroxydopamine activates the mitochondrial apoptosis pathway through p38 MAPK‐mediated, p53‐independent activation of Bax and PUMA
Authors: Gomez‐Lazaro Maria , Galindo Maria F. , Concannon Caoimhín G. , Segura Miguel F. , Fernandez‐Gomez Francisco J. , Llecha Nuria , Comella Joan X. , Prehn Jochen H. M. , Jordan Joaquin
Published: February 2008

J. Neurochem. (2008) 104, 1599–1612.

Mitochondrial alterations have been associated with the cytotoxic effect of 6‐hydroxydopamine (6‐OHDA), a widely used toxin to study Parkinson’s disease. In previous work, we have demonstrated that 6‐OHDA increases mitochondrial membrane permeability leading to cytochrome c release, but the precise mechanisms involved in this process remain unknown. Herein we studied the mechanism of increased mitochondrial permeability of SH‐SY5Y neuroblastoma cells in response to 6‐OHDA. Cytochrome c release induced by 6‐OHDA occurred, in both SH‐SY5Y cells and primary cultures, in the absence of mitochondrial swelling or a decrease in mitochondrial calcein fluorescence, suggesting little involvement of the mitochondrial permeability transition pore in this process. In contrast, 6‐OHDA‐induced cell death was associated with a significant translocation of the pro‐apoptotic Bax protein from the cytosol to mitochondria and with a significant induction of the BH3‐only protein PUMA. Experiments in mouse embryonic fibroblasts deficient in Bax or PUMA demonstrated a role for both proteins in 6‐OHDA‐induced apoptosis. Although 6‐OHDA elevated both total and nuclear p53 protein levels, activation of p53 was not essential for subsequent cell death. In contrast, we found that p38 mitogen‐activated protein kinase (MAPK) was activated early during 6‐OHDA‐induced apoptosis, and that treatment with the p38 MAPK inhibitor SKF86002 potently inhibited PUMA induction, green fluorescent protein‐Bax redistribution and apoptosis in response to 6‐OHDA. These data demonstrate a critical involvement of p38 MAPK, PUMA, and Bax in 6‐OHDA‐induced apoptosis.
Measuring and Motivating Quantity, Creativity, or Both
Authors: KACHELMEIER STEVEN J. , REICHERT BERNHARD E. , WILLIAMSON MICHAEL G.
Published: February 2008

We examine how worker productivity differs when compensation is based on quantity, creativity, or the product of both measures. In an experiment in which participants design “rebus puzzles,” we find that combining quantity and creativity measures in a creativity‐weighted pay scheme results in creativity‐weighted productivity scores that are significantly lower than those generated by participants with quantity incentives alone. Follow‐up analysis indicates that relative to participants in the quantity‐only condition, participants in the creativity‐weighted condition produce approximately the same number of high‐creativity puzzles, but produce significantly fewer puzzles overall. Thus, while participants rewarded for creativity‐weighted output tend to restrict their production to high‐creativity efforts, they are unable to translate this focus into a greater volume of high‐creativity output. Implications address a possible explanation for firms' reluctance to incorporate creativity measures within multidimensional performance measurement systems, notwithstanding published suggestions to do so.
Marking‐to‐Market: Panacea or Pandora's Box?
Authors: PLANTIN GUILLAUME , SAPRA HARESH , SHIN HYUN SONG
Published: February 2008

Financial institutions have been at the forefront of the debate on the controversial shift in international standards from historical cost accounting to mark‐to‐market accounting. We show that the trade‐offs at stake in this debate are far from one‐sided. While the historical cost regime leads to some inefficiencies, marking‐to‐market may lead to other types of inefficiencies by injecting artificial risk that degrades the information value of prices, and induces suboptimal real decisions. We construct a framework that can weigh the pros and cons. We find that the damage done by marking‐to‐market is greatest when claims are (1) long–lived, (2) illiquid, and (3) senior. These are precisely the attributes of the key balance sheet items of banks and insurance companies. Our results therefore shed light on why banks and insurance companies have been the most vocal opponents of the shift to marking‐to‐market.
Politics and Society in The Gambia since Independence
Authors: Perfect David
Published: February 2008

This article examines politics in The Gambia since it achieved its independence from Britain in 1965. The Gambia was the longest continuously surviving multi‐party democracy in Africa until a successful military coup in 1994, with civilian rule being restored in 1996. The article explores political developments under its two post‐colonial leaders, Sir Dawda Jawara (1965–94) and Yahya Jammeh (1994–) in detail, discussing the major Gambian political parties and their performance in national elections; the military coups of 1981 and 1994; and other key events. The overall performance of both governments, in terms of economic and social developments and human rights, is also assessed.
The Socioeconomic Impact of Atopic Dermatitis in the United States: A Systematic Review
Authors: Mancini Anthony J. , Kaulback Kellee , Chamlin Sarah L.
Published: February 2008

Abstract:  The aim of this study was to review studies examining the direct and indirect costs of atopic dermatitis in the United States. A search was performed using OVID MEDLINE, MEDLINE In‐Process and Other Non‐Indexed Citations, EMBASE, the International Agency for Health Technology Assessment (INAHTA) database, and the Cochrane Library. All abstracts were reviewed for the following criteria: original cost data, studies performed in the United States, and English language. The search yielded 418 papers. Fifty‐nine papers were reviewed in detail, and four studies were found that met the inclusion criteria. These cost‐identification analyses estimated the cost of atopic dermatitis heterogeneously and could not be compared directly. National cost estimates ranged widely, from $364 million to $3.8 billion US dollars per year. The cost of atopic dermatitis is significant and will likely increase in proportion to increasing disease prevalence. Measurement of the cost of atopic dermatitis in the United States has been limited to direct cost‐identification analyses, with few studies measuring the indirect cost of disease.
A Study of Targeted Enhanced Patient Care for Pediatric Atopic Dermatitis (STEP PAD)
Authors: Shaw Maren , Morrell Dean S. , Goldsmith Lowell A.
Published: February 2008

Abstract:  Atopic dermatitis is a common chronic skin condition in children. Treatment strategies often require stringent adherence to skin care regimens for symptom resolution. As many factors influence the course of the condition, we investigated the role of a designated “atopic dermatitis educator” in a pediatric dermatology clinic. We planned to determine whether the individual interaction with an atopic dermatitis educator affects the course of disease severity, resolution, and quality of life in atopic children. New and return pediatric atopic dermatitis patients from English‐speaking families were recruited from a pediatric dermatology clinic with a single pediatric dermatologist. The 151 subjects were randomized to either the control or the intervention group. A total of 106 subjects completed the study. Those in the intervention group received the atopic dermatitis educator’s individual counseling/education session. Subjects’ severity was determined by the Scoring Atopic Dermatitis severity index and quality of life by either the Children’s Dermatology Life Quality Index or the Infants’ Dermatitis Quality of Life index depending on the patient’s age. Analysis of covariance was measured. No significant difference was found in the percentage change of severity or quality of life between the groups.