bluuebunny/crossref_metadata_2025 huggingface dataset:
Sertoli Cell Expression of Steroidogenic Acute Regulatory Protein-Related Lipid Transfer 1 and 5 Domain-Containing Proteins and Sterol Regulatory Element Binding Protein-1 Are Interleukin-1β Regulated by Activation of c-Jun N-Terminal Kinase and Cyclooxygenase-2 and Cytokine Induction
Authors: Ishikawa Tomomoto , Hwang Keumsil , Lazzarino Deborah , Morris Patricia L.
Published: August 2005

In testicular Sertoli cells, IL-1β regulates steroid, lactate, and transferrin secretion; although each influences germ cell development and spermatogenesis, little is known about the signaling mechanisms involved. In other cell types, IL-1β potently induces reactive oxygen species and/or cyclooxygenase-2 (COX-2). In contrast, in Sertoli cells, IL-1β does not generate reactive oxygen species, but rapidly phosphorylates c-Jun-NH2-terminal kinase (JNK), but not p44/42 or p38 MAPK. Phosphorylated JNK stimulates COX-2 activity, mediating the expression of ILs and steroidogenic acute regulatory (StAR)-related (StAR-related lipid transfer protein domain containing) proteins D1 and D5, but not D4. In a time- and dose-dependent manner, IL-1β rapidly increases levels of COX-2 mRNA (2-fold); induction of COX-2 protein (50-fold) requires de novo protein synthesis. Concomitantly, increases in IL-1α, IL-6, and IL-1β mRNAs (1–3 h) are observed. As StAR-related lipid transfer protein domain containing protein 1 (StARD1) mRNA decreases, StARD5 mRNA increases; substantial recovery phase induction of StARD1 mRNA above control is noted (24 h). Inhibition of JNK or COX-2 activities prevents IL-1β induction of IL and StARD5 mRNAs and subsequent increases in StARD1 mRNA (24 h), indicating that these effects depend on the activation of both enzymes. StARD1 and D5 protein levels are significantly altered, consistent with posttranscriptional and posttranslational regulation. IL-1β rapidly decreases levels of precursor and mature sterol regulatory element-binding protein-1, changes not altered by cycloheximide, suggesting coordinate regulation of StARD1 and -D5, but not StARD4, expression. These data demonstrate that JNK and COX-2 activities regulate Sertoli cytokines and particularly START domain-containing proteins, suggesting protective stress responses, including transcription and protein and lipid regulation, within this specialized epithelium.
Hepatic Peroxisomal Fatty Acid β-Oxidation Is Regulated by Liver X Receptor α
Authors: Hu Tonghuan , Foxworthy Patricia , Siesky Angela , Ficorilli James V. , Gao Hong , Li Shuyu , Christe Michael , Ryan Timothy , Cao Guoqing , Eacho Patrick , Michael M. Dodson , Michael Laura F.
Published: August 2005

Peroxisomes are the exclusive site for the β-oxidation of very-long-chain fatty acids of more than 20 carbons in length (VLCFAs). Although the bulk of dietary long-chain fatty acids are oxidized in the mitochondria, VLCFAs cannot be catabolized in mitochondria and must be shortened first by peroxisomal β-oxidation. The regulation of peroxisomal, mitochondrial, and microsomal fatty acid oxidation systems in liver is mediated principally by peroxisome proliferator-activated receptor α (PPARα). In this study we provide evidence that the liver X receptor (LXR) regulates the expression of the genetic program for peroxisomal β-oxidation in liver. The genes encoding the three enzymes of the classic peroxisomal β-oxidation cycle, acyl-coenzyme A (acyl-CoA) oxidase, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, are activated by the LXR ligand, T0901317. Accordingly, administration of T0901317 in mice promoted a dose-dependent and greater than 2-fold increase in the rate of peroxisomal β-oxidation in the liver. The LXR effect is independent of PPARα, because T0901317-induced peroxisomal β-oxidation in the liver of PPARα-null mice. Interestingly, T0901317-induced peroxisomal β-oxidation is dependent on the LXRα isoform, but not the LXRβ isoform. We propose that induction of peroxisomal β-oxidation by LXR agonists may serve as a counterregulatory mechanism for responding to the hypertriglyceridemia and liver steatosis that is promoted by potent LXR agonists in vivo; however, additional studies are warranted.
Death Ligand Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis
Authors: Wang Su He , Cao Zhengyi , Wolf Julie M. , Van Antwerp Mary , Baker James R.
Published: August 2005

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice. One week later, the recipient mice were treated with recombinant TRAIL or a control protein. Compared with control animals, TRAIL-treated mice developed a milder form of the disease with a significant decrease in mononuclear cell infiltration in the thyroid and less thyroid follicular destruction. Furthermore, the number of apoptotic thyrocytes and also thyroglobulin-specific T helper-1 cell responses in TRAIL-treated mice was lower than that in the control animals. This study suggests that exogenous TRAIL suppresses the development of autoimmune thyroiditis via altering the function of cells involved in the immune response. These findings may contribute toward a novel treatment autoimmune thyroiditis.
Expression and Regulation of Progestin Membrane Receptors in the Rat Corpus Luteum
Authors: Cai Zailong , Stocco Carlos
Published: August 2005

Despite evidence strongly supporting progesterone’s autocrine actions in the rat corpus luteum (CL), classical progesterone receptors (PR) have not been detected in this gland. Alternatively, in several other systems, progestins have been reported to activate nongenomic pathways via putative progestin membrane receptors (PMRs). The aim of this investigation was to determine whether rat CL membranes bind progestins and contain PMR homologs and whether these proteins are expressed during CL development in a manner that parallels luteal function. We found that luteal cell membranes specifically bind progesterone. Low levels of progesterone and 20α-dihydroprogesterone decreased binding of [3H]progesterone, whereas androstenedione, 17α-hydroxyprogesterone, and pregnenolone were less potent. Other steroids, including corticosterone, mifepristone, and estradiol, were ineffective. We found that the rat CL expresses five genes previously postulated to encode for putative PMRs: PMRα, PMRβ, PMRγ, PR membrane component 1 (PRMC1), and Rda288. Pmrα, Pmrγ, and Prmc1 transcripts rose steadily during pregnancy whereas Pmrβ and Rda288 remained constant. Just before parturition, concomitant with falling progesterone levels, Pmrα, Pmrβ, and Prmc1 decreased. Luteal PMRα and PRMC1 protein levels were lower in samples taken at the end of pregnancy compared with midpregnancy samples. Ergocriptine, which inhibits the secretion of prolactin, the primary luteotrophic hormone in the rat CL, reduced Pmrα, Pmrβ, and Prmc1 expression significantly. Ergocriptine effects were prevented by coadministration of prolactin. These findings provide evidence for the expression and regulation of putative membrane-bound progestin-binding proteins in the rat CL, a tissue that does not express detectable levels of nuclear progesterone receptors.
Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice
Authors: Perwad Farzana , Azam Nasreen , Zhang Martin Y. H. , Yamashita Takeyoshi , Tenenhouse Harriet S. , Portale Anthony A.
Published: August 2005

Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a−/−), and Hyp mice diets containing varying Pi contents (0.02–1.65%). In WT mice, increases in dietary Pi intake from 0.02–1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum Pi concentrations. Across the range of dietary Pi, serum FGF-23 concentrations varied directly with serum Pi concentrations (r2 = 0.72; P < 0.001). In Npt2a−/− mice, serum FGF-23 concentrations were significantly lower than in WT mice, and these differences could be accounted for by the lower serum Pi levels in Npt2a−/− mice. The serum concentrations of FGF-23 in Hyp mice were 5- to 25-fold higher than values in WT mice, and the values varied with dietary Pi intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% Pi diet; in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) Pi diet. In WT mice fed the low (0.02%) Pi diet, renal mitochondrial 1α-hydroxylase activity and renal 1α-hydroxylase (P450c1α) mRNA abundance were significantly higher than in mice fed the higher Pi diets and varied inversely with serum FGF-23 concentrations (r2 = 0.86 and r2 = 0.64; P < 0.001, respectively). The present data demonstrate that dietary Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function. The data suggest that genotype-dependent and dietary Pi-induced changes in the serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.
Endogenous γ-Aminobutyric Acid Can Excite Gonadotropin-Releasing Hormone Neurons
Authors: Moenter Suzanne M. , DeFazio R. Anthony
Published: August 2005

γ-Aminobutyric acid (GABA) provides a major synaptic input to GnRH neurons. GnRH neurons maintain high intracellular chloride levels and respond to exogenous GABA with depolarization and action potential firing. We examined the role of synaptic GABA type A receptor (GABAAR) activation on the firing activity of GnRH neurons. Targeted extracellular recordings were used to detect firing activity of GnRH neurons in brain slices from adult female mice. Because the brain slice preparation preserves both glutamatergic and GABAergic neuronal networks, the effects of GABAARs on GnRH neurons were isolated by blocking ionotropic glutamatergic receptors (iGluR). With iGluR blocked, many GnRH neurons remained spontaneously active. Consistent with an excitatory role for GABA, subsequent blockade of GABAARs suppressed the firing rate in active cells from diestrous females by approximately 40% (P < 0.05; n = 10). GABAAR blockade did not affect inactive cells (n = 7), indicating that GABAAR-mediated inhibition was not responsible for the lack of firing. In prenatally androgenized females, GnRH neurons exhibit larger, more frequent GABAergic postsynaptic currents than control females. Most cells from prenatally androgenized animals fired spontaneously, and the firing rate was suppressed approximately 80% after GABAAR blockade (P < 0.01; n = 8). Blocking GABAAR without blocking iGluRs increased the firing rate in GnRH neurons from diestrous females (P < 0.05; n = 6), perhaps attributable to hyperexcitability within the slice network. Our results indicate that GABAergic inputs help generate a portion of action potentials in GnRH neurons; this fraction depends on the level of GABA transmission and postsynaptic responsiveness. The complexities of the GnRH neuron response to GABA make this a potentially critical integration point for central regulation of fertility.
The Human Na+-Taurocholate Cotransporting Polypeptide Gene Is Activated by Glucocorticoid Receptor and Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α, and Suppressed by Bile Acids via a Small Heterodimer Partner-Dependent Mechanism
Authors: Eloranta Jyrki J. , Jung Diana , Kullak-Ublick Gerd A.
Published: August 2005

Na+-taurocholate cotransporting polypeptide (NTCP) is the major bile acid uptake system in human hepatocytes. NTCP and the ileal transporter ASBT (apical sodium-dependent bile acid transporter) are two sodium-dependent transporters critical for the enterohepatic circulation of bile acids. The hASBT gene is known to be activated by the glucocorticoid receptor (GR). Here we show that GR also induces the endogenous hNTCP gene and transactivates the reporter-linked hNTCP promoter, in the presence of its ligand dexamethasone. Mutational analysis of the hNTCP promoter identified a functional GR response element, with which GR directly interacts within living cells. The GR/dexamethasone activation of endogenous hNTCP expression was suppressed by bile acids, in a manner dependent on the bile acid receptor farnesoid X receptor. Overexpression of the farnesoid X receptor-inducible transcriptional repressor small heterodimer partner also suppressed the GR/dexamethasone-activation of the hNTCP promoter. The peroxisome proliferator-activated receptor-γ coactivator-1α enhanced the GR/dexamethasone activation of the hNTCP promoter. In conclusion, the hNTCP promoter is activated by GR in a ligand-dependent manner, similarly to the hASBT promoter. Thus, glucocorticoids may coordinately regulate the major bile acid uptake systems in human liver and intestine. The GR/dexamethasone activation of the hNTCP promoter is counteracted by bile acids and small heterodimer partner, providing a negative feedback mechanism for bile acid uptake in human hepatocytes.
Three-dimensional Finite Element Analysis of a Semi-Elliptical Circumferential Surface Crack in a Carbon Steel Pipe Subjected to a Bending Moment
Authors: Ligoria S. A , Knight G. M. S , Ramachandra Murthy D. S
Published: August 2005

The study of crack growth is important to evaluate the structural integrity of nuclear power plant piping from the viewpoint of the leak-before-break concept. A thick-walled pipe with a semi-elliptical circumferential surface crack of different initial crack sizes subjected to a bending load is considered for the analysis. A three-dimensional finite element code using ANSYS (Version 8) has been developed with the capability to handle singularity and to evaluate the mode I stress intensity factor based (SIF) on the displacement extrapolation method. The crack growth rate has been calculated by applying the Paris law. The fatigue life predicted for crack penetration through the wall thickness has been compared with that of experimental results in published literature. The deviation is found to be within 17 per cent. Using the finite element model, data in respect of the stress intensity factor for different stresses, thicknesses, crack depths, and half-crack-length conditions have been predicted. Based on the data, a new correlation has been evolved to evaluate the stress intensity factor range in the depth and surface directions. The stress intensity factor has also been calculated by the empirical relations given in the ASM Handbook. The predicted fatigue life using the plate equation deviates from experimental results by a maximum of 77 per cent while the deviation of the prediction using the pipe equation is more than 100 per cent in many cases. The predictions with the proposed correlation give better results that fall within 21 per cent deviation from the experimental results.
Finite Element Simulation of Multipass Welding: Full Three-Dimensional Versus Generalized Plane Strain or Axisymmetric Models
Authors: Jiang W , Yahiaoui K , Hall F R , Laoui T
Published: August 2005

A full three-dimensional (3D) thermo-mechanical finite element (FE) model has been developed to simulate the step-by-step multipass welding process. Non-linearities associated with welding, such as a moving heat source, material deposition, temperature-dependent material properties, latent heat, and large deformations, were taken into account. The model was applied to multipass butt-welded mild steel plate and girth butt-welded stainless steel pipe for validation. The simulation results were compared with independently obtained experimental data and numerical predictions from two-dimensional (2D) generalized plane strain and axisymmetric models. Good agreements between the 3D predictions and experimental data have been obtained. The computational model has the potential to be applied to multipass welded complex geometries for residual stress prediction.
A General Autofrettage Model of a Thick-Walled Cylinder Based on Tensile-Compressive Stress-Strain Curve of a Material
Authors: Huang X. P
Published: August 2005

The basic autofrettage theory assumes elastic-perfectly plastic behaviour. Because of the Bauschinger effect and strain-hardening, most materials do not display elastic-perfectly plastic properties and consequently various autofrettage models are based on different simplified material strain-hardening models, which assume linear strain-hardening or power strain-hardening or a combination of these strain-hardening models. This approach gives a more accurate prediction than the elastic-perfectly plastic model and is suitable for different strain-hardening materials. In this paper, a general autofrettage model that incorporates the material strain-hardening relationship and the Bauschinger effect, based upon the actual tensile-compressive stress-strain curve of a material is proposed. The model incorporates the von Mises yield criterion, an incompressible material, and the plane strain condition. Analytic expressions for the residual stress distribution have been derived.

Experimental results show that the present model has a stronger curve-fitting ability and gives a more accurate prediction. Several other models are shown to be special cases of the general model presented in this paper. The parameters needed in the model are determined by fitting the actual tensile-compressive curve of the material, and the maximum strain of this curve should closely represent the maximum equivalent strain at the inner surface of the cylinder under maximum autofrettage pressure.
Microscopic Strain Mapping Using Scanning Electron Microscopy Topography Image Correlation at Large Strain
Authors: Kang J , Jain M , Wilkinson D. S , Embury J. D
Published: August 2005

Measuring the distribution of local strain at the microscopic level is a challenging problem, especially for materials subjected to large overall strain. In the present study, a novel microscopic strain mapping technique has been developed based on the analysis of surface topography using digital image correlation (DIC) software. The input is a series of scanning electron microscopy (SEM) images. The method uses topographic features (such as surface slip traces) found in these images as the input. A commercially available optical strain measurement system (ARAMIS®, which is a trade name of the equipment from GOM mbH, Braunschweig, Germany) that utilizes the DIC methodology is used for this purpose. It was found that the best results were obtained using an incremental approach in which DIC is used to map the local strain increments following a modest amount of macroscopic deformation. This is essential when using topographic features such as slip traces that are not static. The accuracy and scale of the measurements are affected by image and facet size. The method has been validated, based on in situ deformation of an aluminium alloy within an SEM, using strains measured independently by means of surface indents. The results clearly reveal the details of the local shear on a sub-grain-size scale and the evolution of shear bands within the necking area, leading to local strains that exceed the average strain by a factor of 2.3.
Design, Testing, and Simulation of Fibre Composite Leaf Springs For Heavy Axle Loads
Authors: Hou J P , Cherruault J-Y , Jeronimidis G , Mayer R
Published: August 2005

This paper summarizes the design, manufacturing, testing, and finite element analysis (FEA) of glass-fibre-reinforced polyester leaf springs for rail freight vehicles. FEA predictions of load-deflection curves under static loading are presented, together with comparisons with test results. Bending stress distribution at typical load conditions is plotted for the springs. The springs have been mounted on a real wagon and drop tests at tare and full load have been carried out on a purpose-built shaker rig. The transient response of the springs from tests and FEA is presented and discussed.
Application of the Harmonic Balance Technique to Finite Element Models of Asymmetric Rotors Via Sparse Kronecker Products
Authors: Nandi A , Neogy S , Das A. S
Published: August 2005

Small vibrations of asymmetric rotors with non-axisymmetric shaft and non-isotropic bearings are represented by linear differential equations with periodic coefficients. For computation of a steady state response of the finite element model of these rotors, the present paper proposes a new form of the harmonic balance technique via sparse Kronecker products, which is especially suitable for direct representation in a compact form. This form of harmonic balance technique requires the finite element matrices to be assembled and stored in a compact form using a compact assembler routine. The sparse matrix generated in the harmonic balance technique can then be processed using standard sparse linear system solvers, direct or iterative. The present approach is particularly useful and efficient for large three-dimensional finite element models of rotors with complicated geometries.
A Numerical and Experimental Study of Cavitation in a Hot Tensile Axisymmetric Testpiece
Authors: Liu Y , Lin J , Dean T. A , Farrugia D. C. J
Published: August 2005

During axisymmetric hot tensile testing, necking normally takes place due to the thermal gradient and the accumulation of microdamage. This paper introduces an integrated technique to predict the damage and necking evolution behaviour. Firstly, a set of multiaxial mechanism-based unified viscoplastic-damage constitutive equations is presented. This equation set, which models the evolution of grain boundary (intragranular) and plasticity-induced (intergranular) damage, is determined for a free-cutting steel tested over a range of temperatures and strain rates on a Gleeble thermomechanical simulator. This model has been implemented using the CREEP subroutine of the commercial finite element (FE) solver ABAQUS. Numerical procedures to simulate axisymmetric hot tensile deformation are developed with consideration of the thermal gradient along the axis of the tensile testpiece. FE simulations are carried out to reproduce the necking phenomenon and the evolution of plasticity-induced and grain boundary damage. The simulated results have been validated with experimental tensile test results. The effects of necking and its associated stress state on flow stress and ductility are investigated. The flow stress and ductility data obtained from a Gleeble material simulator under various hot deformation conditions have also been numerically studied.
The Pull-Out Method For On-Site Estimation of the Elastic Modulus of Concrete
Authors: Antonaci P , Bocca P
Published: August 2005

The paper describes a new experimental mechanical method for the on-site evaluation of the elastic modulus of concrete. It is based on a modification of the well-known pull-out test, which is currently used for the estimation of concrete strength. The method consists in pulling out a metal insert embedded in the concrete mass and measuring the force-displacement curve consequent to the extraction. Three displacement transducers were used in order to correctly detect the displacement of the insert. Moreover, an adequate number of loading-unloading cycles was performed in order to stabilize the system and eliminate possible phenomena of mutual sliding between the mechanical parts of the apparatus and between the insert and the concrete mass.

By performing a certain number of pull-out tests the stiffness value of the system is obtained. The material deformability is then estimated through an appropriate correlation curve between pull-out stiffness and elastic modulus, which has been worked out on the basis of finite element simulations and experimental results. The proposed method offers interesting possibilities of application for the characterization of existing structures at affordable costs.
Matching with Contracts
Authors: Hatfield John William , Milgrom Paul R
Published: August 2005

We develop a model of matching with contracts which incorporates, as special cases, the college admissions problem, the Kelso-Crawford labor market matching model, and ascending package auctions. We introduce a new “law of aggregate demand” for the case of discrete heterogeneous workers and show that, when workers are substitutes, this law is satisfied by profit-maximizing firms. When workers are substitutes and the law is satisfied, truthful reporting is a dominant strategy for workers in a worker-offering auction/matching algorithm. We also parameterize a large class of preferences satisfying the two conditions.
How Do Patent Laws Influence Innovation? Evidence from Nineteenth-Century World's Fairs
Authors: Moser Petra
Published: August 2005

Studies of innovation have focused on the effects of patent laws on the number of innovations, but have ignored effects on the direction of technological change. This paper introduces a new dataset of close to fifteen thousand innovations at the Crystal Palace World's Fair in 1851 and at the Centennial Exhibition in 1876 to examine the effects of patent laws on the direction of innovation. The paper tests the following argument: if innovative activity is motivated by expected profits, and if the effectiveness of patent protection varies across industries, then innovation in countries without patent laws should focus on industries where alternative mechanisms to protect intellectual property are effective. Analyses of exhibition data for 12 countries in 1851 and 10 countries in 1876 indicate that inventors in countries without patent laws focused on a small set of industries where patents were less important, while innovation in countries with patent laws appears to be much more diversified. These findings suggest that patents help to determine the direction of technical change and that the adoption of patent laws in countries without such laws may alter existing patterns of comparative advantage across countries.
The Central Role of Noise in Evaluating Interventions That Use Test Scores to Rank Schools
Authors: Chay Kenneth Y , Mcewan Patrick J , Urquiola Miguel
Published: August 2005

Many programs reward or penalize schools based on students' average performance. Mean reversion is a potentially serious hindrance to the evaluation of such interventions. Chile's 900 Schools Program (P-900) allocated resources based on cutoffs in schools' mean test scores. This paper shows that transitory noise in average scores and mean reversion lead conventional estimation approaches to overstate the impacts of such programs. It further shows how a regressiondiscontinuity design can be used to control for reversion biases. It concludes that P-900 had significant effects on test score gains, albeit much smaller than is widely believed
Legislative Bargaining under Weighted Voting
Authors: Snyder James M , Ting Michael M , Ansolabehere Stephen
Published: August 2005

Organizations often distribute resources through weighted voting. We analyze this setting using a noncooperative bargaining game based on the Baron-Ferejohn (1989) model. Unlike analyses derived from cooperative game theory, we find that each voter's expected payoff is proportional to her voting weight. An exception occurs when many high-weight voters exist, as low-weight voters may expect disproportionately high payoffs due to proposal power. The model also predicts that, ex post, the coalition formateur (the party chosen to form a coalition) will receive a disproportionately high payoff. Using data from coalition governments from 1946 to 2001, we find strong evidence of such formateur effects.
Precautionary Saving and Consumption Fluctuations
Authors: Parker Jonathan A , Preston Bruce
Published: August 2005

This paper uses the consumption Euler equation to derive a decomposition of consumption growth into four sources. These four sources are new information, and three sources of predictable consumption growth: intertemporal substitution, changes in the preferences for consumption, and incomplete markets for consumption insurance. Using household-level data, we implement this decomposition for the average growth rate of consumption expenditures on nondurable goods in the United States from 1982 to 1997. The economic importance of precautionary saving rivals that of the real interest rate, but the relative importance of each source of movement in the volatility of consumption is not precisely measured.
Effective Exchange Rates and the Classical Gold Standard Adjustment
Authors: Catão Luis A. V , Solomou Solomos N
Published: August 2005

Using a new international dataset of trade-weighed exchange rates, this paper highlights a neglected adjustment mechanism in the classical gold standard literature. Since gold-pegged countries traded extensively with economies operating more flexible monetary regimes and where parity change was a common adjustment device to systemic shocks, we show that such parity adjustments induced worldwide swings in nominal effective exchange rates. These translated into real exchange rate variations to which trade balances responded with an average elasticity of unity and in the direction of restoring external disequilibria. We conclude that some nominal exchange rate flexibility thus present in the pre-1914 system was instrumental to international payments adjustment.
History, Institutions, and Economic Performance: The Legacy of Colonial Land Tenure Systems in India
Authors: Banerjee Abhijit , Iyer Lakshmi
Published: August 2005

We analyze the colonial land revenue institutions set up by the British in India, and show that differences in historical property rights institutions lead to sustained differences in economic outcomes. Areas in which proprietary rights in land were historically given to landlords have significantly lower agricultural investments and productivity in the post-independence period than areas in which these rights were given to the cultivators. These areas also have significantly lower investments in health and education. These differences are not driven by omitted variables or endogeneity problems; they probably arise because differences in historical institutions lead to very different policy choices.
Incomplete Contracts and the Product Cycle
Authors: Antràs Pol
Published: August 2005

I present a model in which the incomplete nature of contracts governing international transactions limits the extent to which the production process can be fragmented across borders. Because of contractual frictions, goods are initially manufactured in the same country where product development takes place. Only when the good becomes sufficiently standardized is the manufacturing stage of production shifted to a low-wage foreign location. Solving for the optimal organizational structure, I develop a new version of the product cycle hypothesis in which manufacturing is shifted abroad first within firm boundaries, and only at a later stage to independent foreign firms.
Fairness and Redistribution
Authors: Alesina Alberto , Angeletos George-Marios
Published: August 2005

Different beliefs about the fairness of social competition and what determines income inequality influence the redistributive policy chosen in a society. But the composition of income in equilibrium depends on tax policies. We show how the interaction between social beliefs and welfare policies may lead to multiple equilibria or multiple steady states. If a society believes that individual effort determines income, and that all have a right to enjoy the fruits of their effort, it will choose low redistribution and low taxes. In equilibrium, effort will be high and the role of luck will be limited, in which case market outcomes will be relatively fair and social beliefs will be self-fulfilled. If, instead, a society believes that luck, birth, connections, and/or corruption determine wealth, it will levy high taxes, thus distorting allocations and making these beliefs self-sustained as well. These insights may help explain the cross-country variation in perceptions about income inequality and choices of redistributive policies.
Secrecy and Safety
Authors: Daughety Andrew F , Reinganum Jennifer F
Published: August 2005

We provide a model showing that the use of confidential settlement as a strategy for a firm facing tort litigation leads to lower average safety of products sold than would occur if the firm were committed to openness. A rational risk-neutral consumer's response in a market, wherein a firm engages in confidential settlements, may be to reduce demand. A firm committed to openness incurs higher liability and R&D costs, though product demand is not diminished. We identify conditions such that, if the cost of credible auditing (to verify openness) is low enough, a firm prefers to eschew confidentiality.
Homeownership, Community Interactions, and Segregation
Authors: Hoff Karla , Sen Arijit
Published: August 2005

We show that individuals with identical preferences and abilities can self-organize into communities with starkly different civic environments. Specifically, we consider a multi-community city where community quality depends upon residents' efforts to prevent crime, improve local governance, etc. Homeownership raises incentives for such civic efforts, but is beyond the reach of the poor. Within-community externalities lead to segregated cities: the rich reside in healthy homeowner communities, while the poor live in dysfunctional renter communities. Tenure segregation in the United States accords well with our prediction. We study alternative tax-subsidy policies to expand homeownership and to promote integration of homeowners and renters.
Unnatural Selection: Perverse Incentives and the Misallocation of Credit in Japan
Authors: Peek Joe , Rosengren Eric S
Published: August 2005

We examine the misallocation of credit in Japan associated with the perverse incentives faced by banks to provide additional credit to the weakest firms. Firms are more likely to receive additional bank credit if they are in poor financial condition, because troubled Japanese banks have an incentive to allocate credit to severely impaired borrowers in order to avoid the realization of losses on their own balance sheets. This “evergreening” behavior is more prevalent among banks that have reported capital ratios close to the required minimum, and is compounded by the incentives arising from extensive corporate affiliations.
Mediastinitis: a life-threatening complication of acute tonsillitis
Authors: Bell Z , Menezes A A C , Primrose W J , McGuigan J A
Published: August 2005

Acute tonsillitis is a common condition and usually runs a benign course. However life-threatening complications do still occur, even in this postantibiotic era. Infection can spread downwards into the mediastinum through the anatomic cervical spaces, causing widespread cellulitis, necrosis, abscess formation and sepsis. We present a case of descending mediastinitis in an 18-year-old woman, arising from her first episode of tonsillitis and treated successfully by surgical drainage. We believe that an awareness of this complication, early diagnosis using computed tomography scanning, and prompt, adequate surgical drainage will reduce morbidity and mortality.
Oxidative Susceptibility of Unfractionated Serum or Plasma: Response to Antioxidants in Vitro and to Antioxidant Supplementation
Authors: Atkin Mark A , Gasper Amy , Ullegaddi Raj , Powers Hilary J
Published: August 2005

Background: The susceptibility of plasma lipids to oxidation is thought to be a factor contributing to atherogenic risk. Various groups have studied the in vitro oxidizability of isolated LDL and examined the effects of conventional antioxidants. The drawbacks associated with the isolation of LDL for evaluation of in vitro oxidizability, however, have limited the application of this measurement in large-scale studies.

Methods: We developed and evaluated an assay that can be used to directly assess the oxidative susceptibility of unfractionated serum or plasma lipids, obviating the need for isolation of lipoprotein fractions. Oxidative conditions were initiated in vitro with cuprous chloride and 2,2′-azobis(2-amidinopropane) hydrochloride. The effects of antioxidants added in vitro, and as an oral supplement, were monitored by conjugated diene formation.

Results: The addition of ascorbic acid (0–50 μmol/L) in vitro elicited a dose-dependent protective effect, increasing the lag time to oxidation (P <0.001). In contrast, α-tocopherol demonstrated prooxidant behavior at increasing concentrations (0–50 μmol/L), although we observed a decrease in the maximum rate of oxidation. Our findings are supported by the results from plasma samples of participants in a randomized antioxidant (vitamins C and E) intervention study after acute ischemic stroke. The group receiving vitamins C and E for 14 days showed an increased lag time to plasma lipid oxidation in vitro compared with the nonsupplemented group (P <0.05).

Conclusion: The susceptibility of unfractionated plasma or serum lipids to oxidation in vitro offers an alternative to LDL for evaluating the efficacy of antioxidant regimens.
Automated Assay for the Determination of Methylmalonic Acid, Total Homocysteine, and Related Amino Acids in Human Serum or Plasma by Means of Methylchloroformate Derivatization and Gas Chromatography–Mass Spectrometry
Authors: Windelberg Amrei , Årseth Ove , Kvalheim Gry , Ueland Per Magne
Published: August 2005

Background: The combined measurement of methylmalonic acid (MMA) and total homocysteine (tHcy) in serum or plasma is useful in diagnosing and distinguishing between cobalamin and folate deficiencies. We developed and validated an isotope-dilution gas chromatography–mass spectrometry (GC-MS) method with automated sample workup for the determination of MMA, tHcy, and the related amino acids Met, total cysteine (tCys), Ser, and Gly in serum or plasma.

Methods: Serum or plasma samples (100 μL) were treated with a reductant (dithioerythritol), deproteinized with ethanol, and derivatized and extracted in a single step by the addition of methylchloroformate and toluene. All liquid handling was performed in 96-well (1 mL) microtiter plates by a robotic workstation. The N(S)-methoxycarbonyl ethyl ester derivatives were analyzed by GC-MS in the selected-ion monitoring mode.

Results: Detection limits (signal-to-noise ratio, 5:1) were between 0.03 μmol/L (MMA) and 10 μmol/L (Ser, tCys). The assay was linear to 100 μmol/L for MMA and tHcy and to 1000 μmol/L for Met, tCys, Ser, and Gly. The within-day CVs ranged from 0.7% to 3.6% (n = 20), and the between-day CVs from 2.1% to 8.1% (n = 20). The recovery was between 79% and 99% for the different analytes.

Conclusion: This assay combines a simple and automated sample preparation with selective and sensitive GC-MS analysis and is well suited for the combined measurement of MMA, tHcy, and the related amino acids.
A quantitative RT-PCR method to determine topoisomerase I mRNA levels in human tissue samples
Authors: Durand-Faucher Karine , Rabinovitch-Chable Hélène , Dzugan Hélène , Charret Stéphane , Aubry Karine , Genet Dominique , Léobon Sophie , Tubiana-Mathieu Nicole , Cook-Moreau Jeanne , Rigaud Michel , Sturtz Franck G.
Published: August 2005

DNA topoisomerase I (Topo I) is involved in DNA replication, transcription, recombination and repair. Clinical interest has focused on Topo I as it is the molecular target of camptothecin (CPT), used in first and second lines of treatment for different cancer types. Furthermore, it is well demonstrated that the patients who best responded to CPT-based chemotherapy were generally those with the greatest tumoral Topo I expression and/or activity. We developed a sensitive, simple and reproducible method to measure Topo I mRNA expression in human cancer samples. Experiments were performed in two steps. First, we checked the accuracy of the reverse transcription-polymerase chain reaction (RT-PCR) method by testing intra- and interassay reproducibility of
Advanced oxidation protein products in serum of patients with myotonic disease type I: association with serum γ-glutamyltransferase and disease severity
Authors: Siciliano Gabriele , Pasquali Livia , Rocchi Anna , Falorni Michela , Galluzzi Fabio , Rocco Angela , Malvaldi Gino , Pompella Alfonso , Paolicchi Aldo
Published: August 2005

Steinert's disease (myotonic dystrophy type 1; MD) is caused by a CTG trinucleotide expansion on 19q13.3. Although the pathogenic mechanism underlying multisystem involvement in MD is still unclear, a role of oxidative stress in this disease has been suggested. We investigated 39 MD patients to assess the plasma concentration of advanced oxidation protein products (AOPPs) and γ-glutamyltransferase (GGT) and related them to clinical severity scores. Plasma AOPP levels (p=0.021), total serum GGT activity (p=0.0005) and GGT activity associated with low-density lipoprotein (p=0.0021) were significantly higher in patients than in controls. There was significant correlation between serum GGT levels and AOPPs (r=0.5831; p=0.0022). A statistically significant increase in serum GGT with age was found in MD patients (p=0.0193). Receiver operating characteristic curve analysis showed that higher AOPP levels were significantly associated with extra-muscular signs of the disease, i.e., cataracts and heart involvement (area under the curve±SE=0.908±0.083), but not with muscular involvement. The concomitant increment in GGT and AOPPs indicates a possible role of oxidative stress in the pathogenesis of MD type 1, while the association of increased AOPP levels with extra-muscular signs of the disease suggests that individual susceptibility to oxidative stress can modulate the extra-muscular phenotype of the disease.
Allergy testing on the IMMULITE 2000 Random-Access immunoanalyzer – a clinical evaluation study
Authors: Cobbaert Christa M. , Jonker Geert Jan
Published: August 2005

Purpose: We aimed to evaluate the diagnostic performance of the IMMULITE 2000 Allergy System from Diagnostic Products Corporation (DPC) for the detection of inhalant and food allergies, focusing on inhalant and food screens, mixes and single allergens.

Methods: Serum samples were collected from new, unselected patients who were referred to the allergist for a suspected allergy. Patients were classified as study diagnosis-positive for inhalant (food) allergy if they had both a positive clinical examination/history and a positive skin test for inhalant (food) allergy; otherwise – failing one or both of these criteria – they were classified as study diagnosis-negative. Classification and testing of the serum samples was carried out in a blinded fashion. Values greater than 0.35 kU/L were considered positive.

Results: Of the 118 patients included, 63 were considered study diagnosis-positive for inhalation and/or food allergy. DPC inhalation screening showed 82% total agreement (TA) and 91% sensitivity relative to the study diagnoses. The DPC food panel showed 96% TA and 98% specificity relative to the study diagnoses. Relative to specific intracutaneous testing (ICT), the DPC D1, E1 and E5 assays had sensitivity of 82–90%; tree and grass panels had sensitivity of 74% and 95%. The DPC weed panel and initial lots of DPC E5 had poor sensitivity (<40%); mold panel sensitivity was equally low for both DPC and the routinely used Pharmacia assay (36%). Relative to skin prick testing (SPT), specific food allergens had TA of 94–98% and specificity of 95–100%.

Conclusion: In patients classified by the combination of clinical examination/history and skin test results, the DPC IMMULITE 2000 Allergy System generally demonstrated acceptable sensitivity, specificity and TA compared to the study diagnoses, both at the screening level and at the level of panels and single allergens.
Social Problem Solving in Adolescents with Suicidal Behavior: A Systematic Review
Authors: Speckens Anne E. M. , Hawton Keith
Published: August 2005

There is an increasing focus on deficiencies in problem solving as a vulnerability factor for suicidal behavior in general and hence a target for treatment in suicide attempters. In view of the uncertainty of evidence for this in adolescents we conducted a systematic review of the international research literature examining the possible relationship between deficiencies in social problem‐solving skills and suicidal behavior in this population. This was based on searching two electronic databases: Medline 1966 to September 2003 and PsychInfo 1887 to September 2003. Twenty‐two studies of social problem‐solving skills in adolescents with suicidal behavior were found. Most of these studies, which compared adolescent patients with suicide attempts versus either nonsuicidal psychiatric or normal controls, found evidence for problem‐solving deficits in the attempters; however, few of the differences remain after controlling for depression and/or hopelessness. Because most of the studies are cross‐sectional, it is difficult to differentiate between the possibilities that deficiencies in problem‐solving skills lead to depression when adolescents are faced by adversity and hence to suicidal behavior, or whether depression is the main factor which undermines problem‐solving skills. Future research, preferably with longitudinal research designs, is required to determine the nature of the association between problem‐solving skills and suicidal behavior in adolescents. This has important implications for therapeutic interventions.
After the Attempt: Maintaining the Therapeutic Alliance Following a Patient's Suicide Attempt
Authors: Ramsay J. Russell , Newman Cory F.
Published: August 2005

The risk of a patient's suicide is a prominent occupational hazard for psychotherapists. The precise number of patients who attempt suicide while in treatment and then resume therapy with the same therapist is not known, but this situation is a relatively common occurrence in clinical practice. Such scenarios can pose significant challenges to the reestablishment of therapeutic trust and a workable treatment alliance. The aim of this paper is to identify the challenges facing a clinician treating a patient who resumes therapy following a serious suicide attempt, and to offer guidelines for maintaining the viability of the therapeutic alliance.
An Empirical Taxonomy of Social‐Psychological Risk Indicators in Youth Suicide
Authors: Hyde Toni , Kirkland John , Bimler David , Pechtel Pia
Published: August 2005

The current study integrates descriptive (though primarily social‐psychological) statements about youth suicide into a coherent, empirically supported taxonomy. Drawing from relevant literature, a set of 107 items characterizing these contributions about youth suicide was created. Seventy‐two participants sorted these statements according to their “face‐value” by following two separate procedures. Analyses of these two data sets using multi‐dimensional scaling resulted in a common “map” depicting inter‐item (dis)similarities. Non‐arbitrary rotation of this map revealed three bipolar and orthogonal dimensions labelled as under‐ and overengagement, rejection–turmoil, and self‐ to death‐identification. It is suggested this dimensional analysis could provide a viable frame for examining and interpreting descriptions about suicide risk and may serve to extend theoretical accounts.
Income Inequality and Risk of Suicide in New York City Neighborhoods: A Multilevel Case‐Control Study
Authors: Miller Jeffrey R. , Piper Tinka Markham , Ahern Jennifer , Tracy Melissa , Tardiff Kenneth J. , Vlahov David , Galea Sandro
Published: August 2005

Evidence on the relationship between income inequality and suicide is inconsistent. Data from the New York City Office of the Chief Medical Examiner for all fatal injuries was collected to conduct a multilevel case‐control study. In multilevel models, suicide decedents (n = 374) were more likely than accident controls (n = 453) to reside in neighborhoods with greater income inequality even after controlling for individual characteristics; this relation was modified by age with an effect overall and among decedents aged 15–34 but not among decedents 35–64. These data suggest that income inequality may contribute to the risk of suicide in younger adults.