bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergy of combined Doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models
Authors: Cardoso Isabel , Martins Diana , Ribeiro Tania , Merlini Giampaolo , Saraiva Maria João
Published: July 2010

Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special involvement of the peripheral nerve. We had previously shown that doxycycline administered for 3 months at 40 mg/Kg/ml in the drinking water, was capable of removing TTR amyloid deposits present in stomachs of old TTR-V30M transgenic mice; the removal was accompanied by a decrease in extracellular matrix remodeling proteins that accompany fibrillar deposition, but not of non-fibrillar TTR deposition and/or markers associated with pre-fibrillar deposits. On the other hand, Tauroursodeoxycholic acid (TUDCA), a biliary acid, administrated to the same mouse model was shown to be effective at lowering deposited non-fibrillar TTR, as well as the levels of markers associated with pre-fibrillar TTR, but only at young ages.

In the present work we evaluated different doxycycline administration schemes, including different periods of treatment, different dosages and different FAP TTR V30M animal models. Evaluation included CR staining, immunohistochemistry for TTR, metalloproteinase 9 (MMP-9) and serum amyloid P component (SAP). We determined that a minimum period of 15 days of treatment with a 8 mg/Kg/day dosage resulted in fibril removal. The possibility of intermittent treatments was also assessed and a maximum period of 15 days of suspension was determined to maintain tissues amyloid-free. Combined cycled doxycycline and TUDCA administration to mice with amyloid deposition, using two different concentrations of both drugs, was more effective than either individual doxycycline or TUDCA, in significantly lowering TTR deposition and associated tissue markers. The observed synergistic effect of doxycycline/TUDCA in the range of human tolerable quantities, in the transgenic TTR mice models prompts their application in FAP, particularly in the early stages of disease.
Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia: a randomized, double-blind, placebo-controlled, two-center trial
Authors: Park Jae-Woo , Ryu Bongha , Yeo Inkwon , Jerng Ui-Min , Han Gajin , Oh Sunghwan , Lee Jinsoo , Kim Jinsung
Published: July 2010

Background

Functional dyspepsia (FD) is characterized by a high prevalence rate and no standard conventional treatments. Alternative therapies, such as herbal formulas, are widely used to treat FD. However, there are inadequate evidences regarding the safety and efficacy of these formulas. Moreover, the mechanisms by which herbal formulas act in the gastrointestinal tract are controversial. In traditional Korean medicine, Banha-sasim-tang has long been one of the most frequently prescribed herbal formulas for treating dyspepsia. The current study is designed to evaluate the efficacy and safety of Banha-sasim-tang for FD patients and to examine whether there will be a significant correlation between cutaneous electrogastrography recordings and dyspeptic symptoms in FD patients, and between changes in gastric myoelectrical activity and improvement in dyspeptic symptoms during Banha-sasim-tang administration.

Methods

This randomized, double-blind, placebo-controlled trial will be performed at two centers and will include a Banha-sasim-tang group and placebo group. Each group will consist of 50 FD patients. Six weeks of administration of Banha-sasim-tang or placebo will be conducted. During the subsequent 2 months, follow-up observations of primary and secondary outcomes will be performed. The primary outcomes are differences as measured on the gastrointestinal symptom scale, and the secondary outcomes are differences as measured on the visual analogue scale for dyspepsia and on the questionnaire for FD-related quality of life. All outcomes will be measured at baseline, at 2, 4, and 6 weeks of treatment, and at the 1 and 2 month follow-up. Cutaneous electrogastrography will be performed and assessed at baseline and at 6 weeks.

Discussion

This trial will provide evidence of the safety and efficacy of Banha-sasim-tang for the treatment for FD. Furthermore, based on the assessment of the relationship between cutaneous electrogastrography recordings and dyspeptic symptoms in this trial, the possibility of clinical applications of cutaneous electrogastrography in the treatment of FD will be elucidated.

Trial Registration

Current Controlled Trials (ISRCTN 51910678); Clinical Trials.gov Identifier: NCT00987805
Neurogenic diabetes insipidus presenting in a patient with subacute liver failure: a case report
Authors: Shankar Hari Manu , Parsons Anthony K , Burroughs Andy K , Shaw Steve , O'Beirne James , Agarwal Banwari
Published: July 2010

Introduction

To the best of our knowledge, this is the first report in the literature of development of neurogenic diabetes insipidus in a patient with subacute liver failure.

Case presentation

A 25-year-old man presented with subacute liver failure. While awaiting a liver transplant, the patient developed cerebral edema, which resulted in neurogenic diabetes insipidus secondary to cerebral edema. The patient died before the liver transplantation could be carried out.

Conclusion

Neurogenic diabetes insipidus is well recognized in the neurosurgical population as a consequence of cerebral edema and increased intracranial pressure, both of which occur commonly in patients with subacute liver failure.
Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer
Authors: Karabulut Bulent , Karaca Burcak , Varol Umut , Muslu Ugur , Cakar Burcu , Atmaca Harika , Kısım Aslı , Uzunoglu Selim , Uslu Ruchan
Published: July 2010

Background

Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA) induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events.

Methods

XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray®which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR), myeloid cell leukemia-1 (MCL-1), tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), TNFRSF1A-associated death domain protein (TRADD).

Results

We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited.

Conclusions

These are the preliminary molecular results of a novel combination treatment of ATRA and zoledronic acid, with fewer side effects as compared to conventional cytotoxic agents. With additional experimental analysis, it may serve as a good option for the treatment of refractory and elderly ovarian cancer patients, for whom there exists very limited choice of treatment.
RNA interference (RNAi) screening approach identifies agents that enhance paclitaxel activity in breast cancer cells
Authors: Bauer Joshua A , Ye Fei , Marshall Clayton B , Lehmann Brian D , Pendleton Christopher S , Shyr Yu , Arteaga Carlos L , Pietenpol Jennifer A
Published: July 2010

Introduction

Paclitaxel is a widely used drug in the treatment of patients with locally advanced and metastatic breast cancer. However, only a small portion of patients have a complete response to paclitaxel-based chemotherapy, and many patients are resistant. Strategies that increase sensitivity and limit resistance to paclitaxel would be of clinical use, especially for patients with triple-negative breast cancer (TNBC).

Methods

We generated a gene set from overlay of the druggable genome and a collection of genomically deregulated gene transcripts in breast cancer. We used loss-of-function RNA interference (RNAi) to identify gene products in this set that, when targeted, increase paclitaxel sensitivity. Pharmacological agents that targeted the top scoring hits/genes from our RNAi screens were used in combination with paclitaxel, and the effects on the growth of various breast cancer cell lines were determined.

Results

RNAi screens performed herein were validated by identification of genes in pathways that, when previously targeted, enhanced paclitaxel sensitivity in the pre-clinical and clinical settings. When chemical inhibitors, CCT007093 and mithramycin, against two top hits in our screen, PPMID and SP1, respectively, were used in combination with paclitaxel, we observed synergistic growth inhibition in both 2D and 3D breast cancer cell cultures. The transforming growth factor beta (TGFβ) receptor inhibitor, LY2109761, that targets the signaling pathway of another top scoring hit, TGFβ1, was synergistic with paclitaxel when used in combination on select breast cancer cell lines grown in 3D culture. We also determined the relative paclitaxel sensitivity of 22 TNBC cell lines and identified 18 drug-sensitive and four drug-resistant cell lines. Of significance, we found that both CCT007093 and mithramycin, when used in combination with paclitaxel, resulted in synergistic inhibition of the four paclitaxel-resistant TNBC cell lines.

Conclusions

RNAi screening can identify druggable targets and novel drug combinations that can sensitize breast cancer cells to paclitaxel. This genomic-based approach can be applied to a multitude of tumor-derived cell lines and drug treatments to generate requisite pre-clinical data for new drug combination therapies to pursue in clinical investigations.
FK506 causes cellular and functional defects in human natural killer cells
Authors: Kim Tae-Jin , Kim Nayoung , Kang Hyoung Jin , Kim Eun-Ok , Kim Sung Tae , Ahn Hyo Seop , Bluestone Jeffrey A , Lee Kyung-Mi
Published: July 2010

FK506-mediated NK cell defects are associated with impaired IL-2 receptor signaling and selective down-regulation of NK receptors.

The role of NK cells in allogeneic HCT has been increasingly appreciated, particularly in the GVL effect. Although FK506 has been used widely to prevent GVHD, its action was considered to be primarily through activated T cells. In this study, we provide direct evidence for the first time that human NK cells are immediate targets of FK506. Our in vivo data from patients undergoing peripheral blood stem cell transplantation or BMT showed a reduced number of NK cells with down-regulated CD25 expression in their peripheral blood compartment. Likewise, FK506 caused profound inhibition of NK cell proliferation in vitro and suppressed NK cytotoxicity and cytokine secretion in response to IL-2. These defects were accompanied by impaired cell clustering and selective down-regulation of adhesion molecules, ICAM-1, CD2, CD49d, and CD58. Furthermore, FK506 specifically inhibited expression of NKG2D, CD48, and DNAM1 receptors without affecting that of 2B4, NKp30, NKp44, and NKp46. As a result, natural cytotoxicity against K562 tumor targets was impaired, while leaving redirected ADCC via 2B4 intact. Finally, FK506-treated NK cells showed impaired IL-2R signaling and inhibition of STAT3. Collectively, these signaling impairments and selective down-regulation of NK receptors by FK506 may underlie the proliferative and functional defects of NK cells. Thus, our data provide a new insight into the mechanism of immunosuppression by FK506, which should be considered to interpret the outcome of graft transplantation.
Mitochondria and Hypoxia‐induced Gene Expression Mediated by Hypoxia‐inducible Factors
Authors: Chavez Angela , Miranda Luis F. , Pichiule Paola , Chavez Juan C.
Published: July 2010

The influence of mitochondrial activity on gene expression programs, particularly those involved in neuroprotection and repair, is likely to play an important role in the pathophysiology of neurodegenerative diseases. One such gene expression program is activated by the cellular pathway that senses a decrease in optimal oxygen levels and leads to activation of a family of transcriptional activators called hypoxia‐inducible factors (HIFs). HIFs are members of the bHLH‐PAS family of transcription factors and are heterodimers composed of HIF‐α and HIF‐β (also known as aryl hydrocarbon receptor nuclear translocator) subunits that bind to canonical DNA sequences (hypoxia‐regulated elements) in the promoters or enhancers of target genes. HIFs activate the expression of more than a hundred genes encoding proteins that regulate cell metabolism, survival, angiogenesis, vascular tone, hematopoiesis, and other functions. There is considerable evidence showing a bidirectional crosstalk between mitochondrial signals and HIF activity. For instance, mitochondrial reactive oxygen species and metabolic substrates from the tricarboxylic acid cycle are implicated in the regulation of the HIF pathway. Conversely, HIF activity leads to the expression of target genes that influence mitochondrial function. In this chapter we will review the complex interactions between mitochondria and the HIF pathway and we will discuss the relevance of this interaction for metabolic adaptation to hypoxia.
‘It's hollow’: the function of pores within myoglobin
Authors: Tomita Ayana , Kreutzer Ulrike , Adachi Shin-ichi , Koshihara Shin-ya , Jue Thomas
Published: July 2010

Despite a century of research, the cellular function of myoglobin (Mb), the mechanism regulating oxygen (O2) transport in the cell and the structure–function relationship of Mb remain incompletely understood. In particular, the presence and function of pores within Mb have attracted much recent attention. These pores can bind to Xe as well as to other ligands. Indeed, recent cryogenic X-ray crystallographic studies using novel techniques have captured snapshots of carbon monoxide (CO) migrating through these pores. The observed movement of the CO molecule from the heme iron site to the internal cavities and the associated structural changes of the amino acid residues around the cavities confirm the integral role of the pores in forming a ligand migration pathway from the protein surface to the heme. These observations resolve a long-standing controversy – but how these pores affect the physiological function of Mb poses a striking question at the frontier of biology.
Scaling for stress similarity and distorted-shape similarity in bending and torsion under maximal muscle forces concurs with geometric similarity among different-sized animals
Authors: Norberg R. Åke , Aldrin Björn S. Wetterholm
Published: July 2010

When geometric similarity, or isometry, prevails among animals of different sizes their form and proportions are similar. Weight increases as the cube of the length dimension, while cross-sectional areas increase as its square, so in load-bearing structural elements the stress, caused by the body weight, increases in direct proportion to the length dimension, both for pure axial loads and for transverse bending and torsional loads. On this account, large body sizes would be expected to set up compensatory selection on the proportions of supporting structures, making them disproportionately thicker as required to maintain similar, size-independent safety factors against breakage. Most previous scaling theories have assumed that the strength of support elements has evolved with respect to loads due to the body weight. But then, from the arguments above, a scaling principle different from the geometric similarity rule would be required in order for safety factors to remain similar among different-sized animals. Still, most comparable animals of ‘similar kind’ scale in accordance with the geometric similarity rule. Here, we instead argue that muscle forces cause much larger loads on structural support elements during maximum performance events (such as during prey capture or escape from predators) than do loads dictated by the body weight (such as during cruising locomotion), and that structural strength therefore might evolve with respect to maximal muscle forces rather than to the body weight. We explore how the transverse and longitudinal lengths of structural support elements must scale to one another, and to muscle transverse length, in order to satisfy each of the following, functionally based, similarity principles for support elements placed in bending, or in torsion, by maximal muscle forces during locomotion: (1) similarity in axial stress, or (2) in torsional shear stress, and (3) similarity in bent shape, or (4) in twisted shape. A dimensional relationship that satisfies all four conditions actually turns out to be the geometric similarity rule. These functional attributes may therefore help to explain the prevalence of geometric similarity among animals. Conformance of different-sized species with the geometric similarity principle has not been directly selected for as such, of course, but may have arisen as a by-product of adaptation in morphological proportions, following upon selection, in each separate species-lineage, for adequate and similar safety factors against breakage, and similar optimal distorted shapes, of structural support elements placed in bending, or in torsion, by maximal muscle forces.
Cuticular plasticization in the tick,Amblyomma hebraeum(Acari: Ixodidae): possible roles of monoamines and cuticular pH
Authors: Kaufman W. Reuben , Flynn Peter C. , Reynolds Stuart E.
Published: July 2010

The degree of plasticization of the alloscutal cuticle of a ‘hard’ (ixodid) tick, Amblyomma hebraeum, and a ‘soft’ (argasid) tick, Ornithodoros moubata, was assessed throughout the blood-feeding period. Cuticle viscosity was calculated from rate of creep of cuticle under constant load using a Maxwell model. Feeding-related plasticization (i.e. increased rate of extension under a constant load) occurred in A. hebraeum but not in O. moubata. Maxwell viscosity of unfed A. hebraeum cuticle was relatively high (~720 GPa s) but was significantly lower in feeding ticks. Small partially fed ticks displayed a viscosity of ~108 GPa s. Still lower values (42 GPa s) were observed in the largest of the engorged ticks. Following cessation of feeding, there was a significant but limited reversal in viscosity back to ~100 GPa s. The water content of cuticle of unfed A. hebraeum (23.4% of wet mass) rose sharply after the onset of feeding and reached a plateau value of 34.0% at a fed/unfed weight ratio of 3 and beyond. Ixodid ticks lay down new endocuticle during the feeding period. The observed increase in cuticle hydration suggests that both old and new cuticles are hydrated during feeding. Monoamines may play an important role in controlling cuticle viscosity. Dopamine (DA) injected into partially fed A. hebraeum caused plasticization. 5-Hydroxytryptamine (serotonin, 5-HT), which induces plasticization in the blood-sucking insect Rhodnius prolixus, had no statistically significant effect on tick cuticle. Octopamine (OA) and tyramine both caused cuticle stiffening (i.e. opposed plasticization). This suggests a possible inhibitory effect but co-injection of OA with DA did not reduce DA-induced plasticization. The mechanism leading to plasticization of tick cuticle may involve a change in cuticular pH. The viscosity of tick cuticle loops was highest at pH 8.0 (389 GPa s) and fell precipitously in the acidic range to a low value of 2.2 GPa s at pH 5.5–5.7. A cuticular pH of ~6.5 would account for the lowest viscosity observed under physiological conditions (42.4 GPa s for large, day 0, engorged ticks). The V-ATPase inhibitor, concanamycin A, was a potent inhibitor of DA-induced plasticization. These results are consistent with a model in which DA acts to cause plasticization through transport of H+ ions into the cuticle. Measurement of cuticular ion (Na+, K+, Ca2+, Mg2+) content did not suggest that plasticization is caused by any of these ions. Taken together, our results suggest that the mechanism of cuticular plasticization in feeding A. hebraeum is related to hydration, and involves the transport of H+ ions into the sub-cuticular space by cells in the hypodermis. Feeding-induced plasticization was not observed in the rapid feeding tick, O. moubata.
Sound transmission and the recognition of temporally degraded sexual advertisement signals in Cope's gray treefrog (Hyla chrysoscelis)
Authors: Kuczynski Michael C. , Vélez Alejandro , Schwartz Joshua J. , Bee Mark A.
Published: July 2010

Acoustic communication signals degrade as they propagate between signalers and receivers. While we generally understand the degrading effects of sound propagation on the structure of acoustic signals, we know considerably less about how receivers make behavioral decisions based on the perception of degraded signals in sonically and structurally complex habitats where communication occurs. In this study of acoustic mate recognition in Cope's gray treefrog, Hyla chrysoscelis (Cope 1880), we investigated how the temporal structure of male advertisement calls was compromised by propagation in a natural habitat and how females responded to stimuli mimicking various levels of temporal degradation. In a sound transmission experiment, we quantified changes in the pulsed structure of signals by broadcasting synthetic calls during active choruses from positions where we typically encountered signalers, and re-recording the signals from positions where we typically encountered potential receivers. Our main finding was that the silent gaps between pulses become increasingly ‘filled in’ by background noise and reverberations as a function of increasing propagation distance. We also conducted female phonotaxis experiments to determine the threshold modulation depth required to elicit recognition of the pulsatile structure of the call. Females were surprisingly tolerant of degraded temporal structure, and there was a tendency for greater permissiveness at lower playback levels. We discuss these results in terms of presumed mechanisms of call recognition in complex environments and the acoustic adaptation hypothesis.
Cooperative Investments and the Value of Contracting
Authors: Che Yeon-Koo , Hausch Donald B
Published: July 2010

Recent articles have shown that contracts can support the efficient outcome for bilateral trade, even in the face of specific investments and incomplete contracting. These studies typically considered “selfish” investments that benefit the investor (e.g., the seller's investment reduces her production costs). We find very different results for “cooperative” investments that directly benefit the investor's partner (e.g., the seller's investment improves the buyer's value of the good). Most importantly, if committing not to renegotiate the contract is impossible, then contracting has no value, i.e., the parties cannot do better than to abandon contracting altogether in favor of ex post negotiation. (JEL C70, J41, K12, L22)
Rules of Thumb versus Dynamic Programming
Authors: Lettau Martin , Uhlig Harald
Published: July 2010

This paper studies decision-making with rules of thumb in the context of dynamic decision problems and compares it to dynamic programming. A rule is a fixed mapping from a subset of states into actions. Rules are compared by averaging over past experiences. This can lead to favoring rules which are only applicable in good states. Correcting this good state bias requires solving the dynamic program. We provide a general framework and characterize the asymptotic properties. We apply it to provide a candidate explanation for the sensitivity of consumption to transitory income. (JEL E00, C63, C61, E21)
An Economic Theory of GATT
Authors: Bagwell Kyle , Staiger Robert W
Published: July 2010

We propose a unified theoretical framework within which to interpret and evaluate the foundational principles of GATT. Working within a general equilibrium trade model, we represent government preferences in a way that is consistent with national income maximization but also allows for the possibility of distributional concerns as emphasized in leading political-economy models. Using this general framework, we establish that GATT's principles of reciprocity and non-discrimination can be viewed as simple rules that assist governments in their effort to implement efficient trade agreements. From this perspective, we argue that preferential agreements undermine GATT's ability to deliver efficient multilateral outcomes. (JEL F02, F13, F15)
Technology, Employment, and the Business Cycle: Do Technology Shocks Explain Aggregate Fluctuations?
Authors: Galí Jordi
Published: July 2010

I estimate a decomposition of productivity and hours into technology and non-technology components. Two results stand out: (a) the estimated conditional correlations of hours and productivity are negative for technology shocks, positive for nontechnology shocks; (b) hours show a persistent decline in response to a positive technology shock. Most of the results hold for a variety of model specifications, and for the majority of G7 countries. The picture that emerges is hard to reconcile with a conventional real-business-cycle interpretation of business cycles, but is shown to be consistent with a simple model with monopolistic competition and sticky prices. (JEL E32, E24)
Endogenous Technological Change and Wage Inequality
Authors: Lloyd-Ellis Huw
Published: July 2010

Although microeconomic studies find a positive relationship between R&D and skill premia, much of the recent rise in U.S. wage inequality was accompanied by slowing labor-productivity growth and relatively slow introduction of new technologies. These conflicting observations are consistent with the effects of a skewed distribution of “absorptive capacities”—the rate at which technology-specific skills can be acquired—in a model of endogenous technological change. The framework is used to assess whether the productivity slowdown and the rise in wage inequality can be jointly accounted for by the contemporaneous decline in the growth rate of labor quality. (JEL E24, J31, O3)
A Schumpeterian Model of Protection and Relative Wages
Authors: Dinopoulos Elias , Segerstrom Paul
Published: July 2010

This paper presents a dynamic general equilibrium model of R&D-based trade between two structurally identical countries in which both innovation and skill acquisition rates are endogenously determined. Trade liberalization increases R&D investment and the rate of technological change. It also reduces the relative wage of unskilled workers and results in skill upgrading within each industry when R&D is the skilled-labor intensive activity relative to manufacturing of final products. Time-series evidence from the United States and simulation analysis support the empirical relevance of the model, which offers a North–North trade explanation for increasing wage inequality. (JEL F10, F12, F13, D32, D41)
The Twin Crises: The Causes of Banking and Balance-of-Payments Problems
Authors: Kaminsky Graciela L , Reinhart Carmen M
Published: July 2010

In the wake of the Mexican and Asian currency turmoil, the subject of financial crises has come to the forefront of academic and policy discussions. This paper analyzes the links between banking and currency crises. We find that: problems in the banking sector typically precede a currency crisis—the currency crisis deepens the banking crisis, activating a vicious spiral; financial liberalization often precedes banking crises. The anatomy of these episodes suggests that crises occur as the economy enters a recession, following a prolonged boom in economic activity that was fueled by credit, capital inflows, and accompanied by an overvalued currency. (JEL F30, F41)
Follow the Leader: Theory and Evidence on Political Participation
Authors: Shachar Ron , Nalebuff Barry
Published: July 2010

Using state-by-state voting data for U.S. presidential elections, we observe that voter turnout is a positive function of predicted closeness. To explain the strategic component of political participation, we develop a follow-the-leader model. Political leaders expend effort according to their chance of being pivotal, which depends on the expected closeness of the race (at both state and national levels) and how voters respond to their effort. Structural estimation supports this model. For example, a 1-percent increase in the predicted closeness at the state level stimulates leaders' efforts, which increases turnout by 0.34 percent. (JEL D72, C33, C72, H41)
Roads to Prosperity? Assessing the Link Between Public Capital and Productivity
Authors: Fernald John G
Published: July 2010

Does the positive correlation between infrastructure and productivity reflect causation? If so, in which direction? I find that when growth in roads (the largest component of infrastructure) changes, productivity growth changes disproportionately in U.S. industries with more vehicles. That vehicle-intensive industries benefit more from road-building suggests that roads are productive. At the margin, however, road investments do not appear unusually productive. Intuitively, the interstate system was highly productive, but a second one would not be. Road-building thus explains much of the productivity slowdown through a one-time, unrepeatable productivity boost in the 1950's and 1960's. (JEL E62, O47, R53)
Do Workplace Smoking Bans Reduce Smoking?
Authors: Evans William N , Farrelly Matthew C , Montgomery Edward
Published: July 2010

In recent years workplace smoking policies have become increasingly prevalent and restrictive. Using data from two large-scale national surveys, we investigate whether these policies reduce smoking. Our estimates suggest that workplace bans reduce smoking prevalence by 5 percentage points and daily consumption among smokers by 10 percent. Although workers with better health habits are more likely to work at firms with smoking bans, estimates from systems of equations indicate that these results are not subject to an omitted variables bias. The rapid increase in bans can explain all of the recent drop in smoking among workers relative to nonworkers. (JEL J28, I18)
The Redesign of the Matching Market for American Physicians: Some Engineering Aspects of Economic Design
Authors: Roth Alvin E , Peranson Elliott
Published: July 2010

We report on the design of the new clearinghouse adopted by the National Resident Matching Program, which annually fills approximately 20,000 jobs for new physicians. Because the market has complementarities between applicants and between positions, the theory of simple matching markets does not apply directly. However, computational experiments show the theory provides good approximations. Furthermore, the set of stable matchings, and the opportunities for strategic manipulation, are surprisingly small. A new kind of “core convergence” result explains this; that each applicant interviews only a small fraction of available positions is important. We also describe engineering aspects of the design process. (JEL C78, B41, J44)
Measuring Duopoly Power in the British Electricity Spot Market
Authors: Wolfram Catherine D
Published: July 2010

This article presents an empirical study of market power in the British electricity industry. Estimates of price-cost markups are derived using direct measures of marginal cost and several approaches that do not rely on cost data. Since two suppliers facing inelastic demand dominate the industry, most oligopoly models predict prices substantially above marginal costs. All estimates indicate that prices, while higher than marginal costs, are not nearly as high as most theoretical models predict. Regulatory constraints, the threat of entry, and financial contracts between the suppliers and their customers are considered as possible explanations for the observed price levels. (JEL L13, L94)
Machine Replacement and the Business Cycle: Lumps and Bumps
Authors: Cooper Russell , Haltiwanger John , Power Laura
Published: July 2010

This paper explores investment fluctuations due to discrete changes in a plant's capital stock. The resulting aggregate investment dynamics are surprisingly rich, reflecting the interaction between a replacement cycle, the cross-sectional distribution of the age of the capital stock, and an aggregate shock. Using plant-level data, lumpy investment is procyclical and more likely for older capital. Further, the predicted path of aggregate investment that neglects vintage effects tracks actual aggregate investment reasonably well. However, ignoring fluctuations in the cross-sectional distribution of investment vintages can yield predictable nontrivial errors in forecasting changes in aggregate investment. (JEL E22, E32)
The Effect of Price Advertising on Prices: Evidence in the Wake of 44 Liquormart
Authors: Milyo Jeffrey , Waldfogel Joel
Published: July 2010

The 44 Liquormart decision, eliminating Rhode Island's ban on liquor price advertising, made Rhode Island the subject of a natural experiment for measuring the effect of advertising on prices. Using Massachusetts prices as controls, we find that advertising stores substantially cut only prices of the products that they advertise. Prices of other products, at both advertising and nonadvertising stores, do not change. Advertising stores cut their prices on products advertised by rivals, while nonadvertising stores do not. We find no reductions in price dispersion across stores. Newspaper-advertising stores appear to draw a higher share of customers after they advertise. (JEL L11, L51, L66)
Bicameralism and Its Consequences for the Internal Organization of Legislatures
Authors: Diermeier Daniel , Myerson Roger B
Published: July 2010

Theories of organization of legislatures have mainly focused on the U.S. Congress, explaining why committee systems emerge there, but not explaining variance in organization across legislatures of different countries. To analyze the effects of different constitutional features on the internal organization of legislatures, we adopt a vote-buying model and consider the incentives to delegate decision rights in a game among legislative chambers. We show how presidential veto power and bicameral separation can encourage a legislative chamber to create internal veto players or supermajority rules, while a unicameral structure can encourage legislators to delegate power to a leader. (JEL D72)
Marginal Tax Rates and Income Inequality in a Life-Cycle Model
Authors: Altig David , Carlstrom Charles T
Published: July 2010

In this paper we study the quantitative impact of marginal tax rates on the distribution of income. Our methodology builds on computable general-equilibrium framework. We find that distortions from marginal tax rate changes of the sort implied by the Tax Reform Act of 1986 have sizable effects on income inequality in a reasonably quantified life-cycle setting: In our model rate changes alone capture half the increase in the pretax Gini that actually occurred between 1984 and 1989. (JEL C68, D31, H30, H20)
Changes in Unemployment and Wage Inequality: An Alternative Theory and Some Evidence
Authors: Acemoglu Daron
Published: July 2010

I present a model where firms decide what types of jobs to create and then search for suitable workers. When there are few skilled workers and the skilled-unskilled productivity gap is small, firms create a single type of job and recruit all workers. An increase in the proportion of skilled workers or skill-biased technical change can create a qualitative change in the composition of jobs, increasing the demand for skills, wage inequality, and unemployment. I provide some evidence that there has been a change in the composition of jobs in the United States during the past two decades. (JEL E24, J31, J64)
Endogenous Inequality in Integrated Labor Markets with Two-Sided Search
Authors: Mailath George J , Samuelson Larry , Shaked Avner
Published: July 2010

We consider a market with “red” and “green” workers, where labels are payoff irrelevant. Workers may acquire skills. Skilled workers search for vacancies, while firms search for workers. A unique symmetric equilibrium exists in which color is irrelevant. There are also asymmetric equilibria in which firms search only for green workers, more green than red workers acquire skills, skilled green workers receive higher wages, and the unemployment rate is higher among skilled red workers. Discrimination between ex ante identical individuals arises in equilibrium, and yet firms have perfect information about their workers, and strictly prefer to hire minority workers. (JEL C70, D40, J30)
Federal Reserve Information and the Behavior of Interest Rates
Authors: Romer Christina D , Romer David H
Published: July 2010

This paper tests for the existence of asymmetric information between the Federal Reserve and the public by examining Federal Reserve and commercial inflation forecasts. It demonstrates that the Federal Reserve has considerable information about inflation beyond what is known to commercial forecasters. It also shows that monetary-policy actions provide signals of the Federal Reserve's information and that commercial forecasters modify their forecasts in response to those signals. These findings may explain why long-term interest rates typically rise in response to shifts to tighter monetary policy. (JEL E52, E43, D82)
Standardization in Decentralized Economies
Authors: Auriol Emmanuelle , Benaim Michel
Published: July 2010

This paper presents a dynamic model, inspired by evolutionary game theory, of how standards and norms emerge in decentralized economies. It shows that standardization outcomes depend on adopters' attitudes to problems caused by incompatibility. If individuals display aversion to incompatibility, standardization never fails to happen eventually, but societies sometimes end up picking inferior standards. In this case, official action can be useful to quickly achieve sensible standardization. On the other hand, when individuals display tolerance or neutrality to incompatibility, there is neither path-dependency nor a lock-in problem, and regulation seems a poor alternative to laissez-faire. (JEL C73, D62, L1)
Orchestrating Impartiality: The Impact of “Blind” Auditions on Female Musicians
Authors: Goldin Claudia , Rouse Cecilia
Published: July 2010

A change in the audition procedures of symphony orchestras—adoption of “blind” auditions with a “screen” to conceal the candidate's identity from the jury—provides a test for sex-biased hiring. Using data from actual auditions, in an individual fixed-effects framework, we find that the screen increases the probability a woman will be advanced and hired. Although some of our estimates have large standard errors and there is one persistent effect in the opposite direction, the weight of the evidence suggests that the blind audition procedure fostered impartiality in hiring and increased the proportion women in symphony orchestras. (JEL J7, J16)
Mentoring and Diversity
Authors: Athey Susan , Avery Christopher , Zemsky Peter
Published: July 2010

We study how diversity evolves at a firm with entry-level and upper-level employees who vary in ability and “type” (gender or ethnicity). The ability of entry-level employees is increased by mentoring. An employee receives more mentoring when more upper-level employees have the same type. Optimal promotions are biased by type, and this bias may favor either the minority or the majority. We characterize possible steady states, including a “glass ceiling,” where the upper level remains less diverse than the entry level. A firm may have multiple steady states, whereby temporary affirmative-action policies have a long-run impact. (JEL J71, J41, D20)
Aid, Policies, and Growth
Authors: Burnside Craig , Dollar David
Published: July 2010

This paper uses a new database on foreign aid to examine the relationships among foreign aid, economic policies, and growth of per capita GDP. We find that aid has a positive impact on growth in developing countries with good fiscal, monetary, and trade policies but has little effect in the presence of poor policies. Good policies are ones that are themselves important for growth. The quality of policy has only a small impact on the allocation of aid. Our results suggest that aid would be more effective if it were more systematically conditioned on good policy. (JEL F350, O230, O400)
Meetings with Costly Participation
Authors: Osborne Martin J , Rosenthal Jeffrey S , Turner Matthew A
Published: July 2010

We study a collective decision-making process in which people interested in an issue may participate, at a cost, in a meeting, and the resulting decision is a compromise among the participants' preferences. We show that the equilibrium number of participants is small and their positions are extreme, and when the compromise is the median, the outcome is likely to be random. The model and its equilibria are consistent with evidence on the procedures and outcomes of U.S. regulatory hearings. (JEL D7, H0, L5)
Motivating Wealth-Constrained Actors
Authors: Lewis Tracy R , Sappington David E. M
Published: July 2010

We examine how owners of productive resources (e.g., public enterprises or financial capital) optimally allocate their resources among wealth-constrained operators of unknown ability. Optimal allocations exhibit: (1) shared enterprise profit—the resource owner always shares the operator's profit; (2) dispersed enterprise ownership—resources are widely distributed among operators of varying ability; (3) limited benefits of competition—the owner may not benefit from increased competition for the resource; and, sometimes, (4) diluted incentives for the most capable—more capable operators receive smaller shares of the returns they generate. Implications for privatizations and venture capital arrangements are explored. (JEL D82, D44, D20)
Schooling, Labor-Force Quality, and the Growth of Nations
Authors: Hanushek Eric A , Kimko Dennis D
Published: July 2010

Direct measures of labor-force quality from international mathematics and science test scores are strongly related to growth. Indirect specification tests are generally consistent with a causal link: direct spending on schools is unrelated to student performance differences; the estimated growth effects of improved labor-force quality hold when East Asian countries are excluded; and, finally, home-country quality differences of immigrants are directly related to U.S. earnings if the immigrants are educated in their own country but not in the United States. The last estimates of micro productivity effects, however, introduce uncertainty about the magnitude of the growth effects. (JEL O40, I20, J24)
“Globalization” and Vertical Structure
Authors: McLaren John
Published: July 2010

This paper analyzes the effects of international openness on vertical integration. Vertical integration can confer a negative externality, by thinning the market for inputs and thus worsening opportunism problems; this induces strategic complementarity and multiple equilibria in the integration decision, thus providing a theory of different “industrial systems” or “industrial cultures” in ex ante identical countries. International openness thickens the market, facilitating leaner, less integrated firms, thus providing gains from international openness quite different from those that are familiar from trade theory. This may be taken as one theory of “outsourcing,” “downsizing,” and “Japanization” as consequences of “globalization.” (JEL D23, F15, L22)
Which Inequality? The Inequality of Endowments versus the Inequality of Rewards
Authors: Hopkins Ed , Kornienko Tatiana
Published: July 2010

We introduce a new distinction between inequality in initial endowments (e.g., ability, inherited wealth) and inequality of what one can obtain as rewards (e.g., prestigious positions, money). We show that, when society allocates resources via tournaments, these two types of inequality have opposing effects on equilibrium behavior and well-being. Greater inequality of rewards hurts most people—both the middle class and the poor—who are forced into greater effort. Conversely, greater inequality of endowments benefits the middle class. Thus, the correctness of our intuitions about the implications of inequality is hugely affected by the type of inequality considered. (JEL D63, D82)
Money, Political Ambition, and the Career Decisions of Politicians
Authors: Keane Michael P , Merlo Antonio
Published: July 2010

We assess the impact of a variety of policies that may influence the career decisions of members of the US Congress. These policies alter incentives to run for re-election, run for higher office or leave Congress, by altering wages, non-pecuniary rewards and career prospects (both in and out of Congress). We find that the effect of most policies varies considerably across different types of politicians. For example, a reduction in the congressional wage would disproportionately induce exit from Congress by “skilled” politicians, Democrats, and politicians who were relatively young when first elected, but not by politicians who most value legislative accomplishments (“achievers”). (JEL D72)
“Bricks and Clicks”: The Impact of Product Returns on the Strategies of Multichannel Retailers
Authors: Ofek Elie , Katona Zsolt , Sarvary Miklos
Published: July 2010

The Internet has increased the flexibility of retailers, allowing them to operate an online arm in addition to their physical stores. The online channel offers potential benefits in selling to customer segments that value the convenience of online shopping, but it also raises new challenges. These include the higher likelihood of costly product returns when customers' ability to “touch and feel” products is important in determining fit. We study competing retailers that can operate dual channels (“bricks and clicks”) and examine how pricing strategies and physical store assistance levels change as a result of the additional Internet outlet. A central result we obtain is that when differentiation among competing retailers is not too high, having an online channel can actually increase investment in store assistance levels (e.g., greater shelf display, more-qualified sales staff, floor samples) and decrease profits. Consequently, when the decision to open an Internet channel is endogenized, there can exist an asymmetric equilibrium where only one retailer elects to operate an online arm but earns lower profits than its bricks-only rival. We also characterize equilibria where firms open an online channel, even though consumers only use it for research and learning purposes but buy in stores. A number of extensions are discussed, including retail settings where firms carry multiple product categories, shipping and handling costs, and the role of store assistance in impacting consumer perceived benefits.