bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of Ships with Water on Deck in Random Beam Waves
Authors: Liqin Liu , Yougang Tang
Published: March 2007

We study the stability of small ships with water on deck in random beam waves from a probability perspective. Previous research has shown that this kind of ship motion is governed by two dynamical regions: Homoclinic and heteroclinic, where the heteroclinic model emulates symmetric vessel capsize and the homoclinic model represents a vessel with an initial bias caused by water on deck. We investigate the stability and capsizing of ships in the homoclinic region using the probability method and nonlinear stochastic dynamics theory. Simplifying the random wave excitation to a periodic force and white noise perturbation, the random Melnikov mean square criterion is used to determine the parameter domain for the ship's stochastic chaotic motion. The probability density function of the roll response is calculated by solving the stochastic differential equations using the path integral method. A mathematical example is presented. It is found that in the chaotic parameter region, the probability density function of the system has two peaks. The response of the system will jump from one peak to another for large amplitudes of periodic excitation. This will lead to instability and even capsizing.
A Modal Filtering and Statistical Approach for Damage Detection and Diagnosis in Structures using Ambient Vibrations Measurements
Authors: Bahlous S. El-Ouafi , Abdelghani M. , Smaoui H. , El-Borgi S.
Published: March 2007

The monitoring and diagnosis of structures using output-only ambient vibration tests are becoming increasingly popular nowadays. In this Article a new statistics-based approach is proposed for damage detection and diagnosis (localization and quantification) in structures under their normal working conditions. The proposed approach requires vibration data relative to the current and reference states of the structure as well as a finite element model parameterized using specified damage parameters. Such parameters may include physical and/or geometrical properties of the structure. Modal filtering, combined with an asymptotic local approach, is used to compute an improved residual which turns out to be normally distributed. The mean, covariance and sensitivity of this residual allow the detection of damage based on generalized log-likelihood ratio (GLR) tests. The diagnosis of damage is made possible by applying sensitivity and rejection tests to the residual vector computed directly from the finite element model. Constraints on the damage parameters are also incorporated into these test statistics to ensure that only physically feasible damage is considered. Moreover, in some cases of multiple damage, a branch-and-bound scheme may be necessary to expedite the search for damage. The proposed damage detection and diagnosis algorithm is tested on simulation examples of simple structures.
Neural Net-based Modeling and Control of a Micro-positioning Platform Using Piezoelectric Actuators
Authors: Liu Van-Tsai , Huang Hsiang-Chan , Lin Chun-Liang , Jian Zi-Jie
Published: March 2007

The paper proposes an integrated controller which combines feedforward, PID and a cross-coupling controller to achieve high accuracy for a dual-axis piezoelectric actuated platform. A Preisach model is created to numerically describe the hysteresis behavior of the piezoelectric actuators. On the basis of the Preisach model, a feedforward compensator is developed to compensate for the hysteresis nonlinearity. A PID controller is introduced to further suppress the tracking error due to the modeling inaccuracy and hence to obtain precision tracking control. Finally, a neural net-based cross-coupling control scheme is proposed to reduce the contour errors, which are very typical in dual-axis tracking control problems. The approach developed is numerically and experimentally verified with a variety of operating conditions.
Images in the aftermath of trauma: Responding to September 11th
Authors: Young Alison
Published: March 2007

An event such as the attack on Manhattan on September 11th 2001 is socially, culturally and politically traumatizing. Those who saw the attack (in person or through media coverage) emphasized its visual impact. Faced with such visual trauma, it is unsurprising that the aftermath of the attacks had a representational dimension, as individuals and institutions strove to suture the resulting wound through image making. This article investigates the legacy of visual trauma after September 11th in the difficult interim years when disaster is no longer part of the immediate past. I focus on two texts (the Final Report of the National Commission on Terrorist Attacks upon the United States, or 9/11 Report, and a short film by the Mexican director, Alejandro González Iñárritu), each of which displays in different ways the effects of the trauma of witnessing disaster. The aim is to raise questions about the legacy of traumatic events for the legal and cultural responses which follow in their wake, and to that extent the article thinks through the demands of witnessing trauma, the ethical challenges for the cinematic documentation of a traumatic event, and the limits upon judgment in the aftermath of disaster.
Potential spaces of crime: The playful, the destructive, and the distinctively human
Authors: Williams Christopher R.
Published: March 2007

Though most share an interest in answering the question, ‘What are people trying to accomplish when they commit a crime?’ criminologists have been largely reluctant to entertain the ways in which the accomplishment of crime reflects deeper, more fundamental and distinctively human capacities and needs. Of especial significance in this context are the human capacity and need for creative engagement. The interplay between human ontology, experience, and behavior gives rise to a variety of such expressions and engagements, both normative and illicit in manifestation. Where history, culture, organization, and biography erect limitations, human beings can be expected to seek out or construct alternative, at times playful and at times destructive, experiential spaces for creative engagement. Drawing from cultural criminology, existentialism, and critical humanism, these spaces are provisionally explored.
CSI and moral authority: The police and science
Authors: Cavender Gray , Deutsch Sarah K.
Published: March 2007

Since it first aired in 2000, CSI has consistently been among the top-rated television programs in the United States. In this article, we analyze CSI’s debut season and also include observations about the program today as well as its two spin-offs: CSI: NY and CSI: Miami. We are interested in the cultural meanings conveyed in this very popular forensic crime drama, especially in terms of the moral authority of the police and of science. We consider how CSI uses the conventions of the crime genre to assert the police as a moral authority. We also demonstrate how CSI portrays a sense of forensic realism, and, in so doing, asserts the veracity of science. We conclude with a discussion of what these meanings suggest about the legitimacy of policing and of science.
Cultural criminology and primitive accumulation: A formal introduction for two strangers who should really become more intimate
Authors: Hall Steve , Winlow Simon
Published: March 2007

In this brief polemic we argue that a renewed critical approach to the destructive power of capitalism is essential for criminological theory. The current focus on the allegedly plural and transgressive sub-cultural foreground of criminality has drawn our attention away from the restrictive and constitutive politico-cultural power that the mutating ‘deep structure’ of capitalism wields over contemporary social life. Rather than delve into the hapless post-political worlds of inter-subjectivity, relativism and micro-exotica in the expectation of finding organic forms of ‘resistance’, yield ground to cynical actuarialism and retreat from serious critical reasoning, 21st-century criminology must take a step forward in addressing the increasingly competitive, anxious and criminogenic culture of advanced capitalism as it enters a revived and notably brutal phase of primitive accumulation. It can do this by tightening its empirical focus, strengthening its theoretical approach and deepening its philosophical foundations.
Activation mechanisms of STAT5 by oncogenic Flt3-ITD
Authors: Choudhary Chunaram , Brandts Christian , Schwable Joachim , Tickenbrock Lara , Sargin Bülent , Ueker Andrea , Böhmer Frank-D. , Berdel Wolfgang E. , Müller-Tidow Carsten , Serve Hubert
Published: March 2007

Mutations in the receptor tyrosine kinase Flt3 represent a very common genetic lesion in acute myeloid leukemia (AML). Internal tandem duplication (ITD) mutations clustered in the juxtamembrane domain are the most frequent and best characterized mutations found in Flt3. Oncogenic activation of Flt3 by ITD mutations is known to activate aberrant signaling including activation of STAT5 and repression of myeloid transcription factors Pu.1 and c/EBP-alpha. However, the mechanisms of STAT5 activation by Flt3-ITD remain unclear. Using small molecule inhibitors and cell lines deficient for Src family kinases or Jak2 or Tyk2, here we show that Flt3-ITD–induced STAT5 activation is independent of Src or Jak kinases. Also, overexpression of SOCS1, an inhibitor of Jak kinases, inhibited IL-3– but not Flt3-ITD–mediated STAT5 activation. Furthermore, in vitro kinase assays revealed that STAT5 is a direct target of Flt3. Taken together, our data provide the mechanistic basis of STAT5 activation by Flt3-ITD.
Different chromosomal breakpoints impact the level of LMO2 expression in T-ALL
Authors: Dik Willem A. , Nadel Bertrand , Przybylski Grzegorz K. , Asnafi Vahid , Grabarczyk Piotr , Navarro Jean Marc , Verhaaf Brenda , Schmidt Christian A. , Macintyre Elizabeth A. , van Dongen Jacques J. M. , Langerak Anton W.
Published: March 2007

The t(11;14)(p13;q11) is presumed to arise from an erroneous T-cell receptor delta TCRD V(D)J recombination and to result in LMO2 activation. However, the mechanisms underlying this translocation and the resulting LMO2 activation are poorly defined. We performed combined in vivo, ex vivo, and in silico analyses on 9 new t(11;14)(p13;q11)-positive T-cell acute lymphoblastic leukemia (T-ALL) as well as normal thymocytes. Our data support the involvement of 2 distinct t(11;14)(p13;q11) V(D)J-related translocation mechanisms. We provide compelling evidence that removal of a negative regulatory element from the LMO2 locus, rather than juxtaposition to the TCRD enhancer, is the main determinant for LMO2 activation in the majority of t(11;14)(p13;q11) translocations. Furthermore, the position of the LMO2 breakpoints in T-ALL in the light of the occurrence of TCRD-LMO2 translocations in normal thymocytes points to a critical role for the exact breakpoint location in determining LMO2 activation levels and the consequent pressure for T-ALL development.
The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia
Authors: Mohty Mohamad , Yong Agnes S. M. , Szydlo Richard M. , Apperley Jane F. , Melo Junia V.
Published: March 2007

Because the polycomb group gene BMI1 regulates the proliferation of both normal and leukemic stem cells, we examined whether BMI1 expression was associated with disease progression in chronic myeloid leukemia (CML). Levels of BMI1 RNA were significantly higher in patients with advanced-phase than in patients with chronic-phase CML in both CD34+ cells (P = .006) and total peripheral-blood mononuclear cells (P < .001). E2F1, a transcription factor regulating BMI1, was up-regulated in CML compared with controls (P = .001). In a cohort of 64 CML patients, the level of BMI1 at diagnosis correlated with time to transformation to blast crisis, and the combination of low BMI1 and high proteinase-3 expression was associated in multivariate analysis with an improved overall survival (P = .001). We conclude that BMI1 may be a biomarker for the intrinsic heterogeneity of CML, and its measurement at diagnosis can help predict overall survival and thus contribute to better therapeutic decisions.
Functional Analysis of Monocarboxylate Transporter 8 Mutations Identified in Patients with X-Linked Psychomotor Retardation and Elevated Serum Triiodothyronine
Authors: Jansen Jurgen , Friesema Edith C. H. , Kester Monique H. A. , Milici Carmelina , Reeser Maarten , Grüters Annette , Barrett Timothy G. , Mancilla Edna E. , Svensson Johan , Wemeau Jean-Louis , Busi da Silva Canalli Maria Heloisa , Lundgren Johan , McEntagart Meriel E. , Hopper Neil , Arts Willem Frans , Visser Theo J.
Published: March 2007

Context: T3 action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T3 uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T3 levels.

Objective: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T3.

Design: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T3 uptake, 2) T3 metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry.

Results: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8.

Conclusion: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T3 levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T3 in central neurons.
Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition
Authors: Pereira Rossana M. C. , Aguiar-Oliveira Manuel H. , Sagazio Alessia , Oliveira Carla R. P. , Oliveira Francielle T. , Campos Viviane C. , Farias Catarine T. , Vicente Tábita A. R. , Gois Miburge B. , Oliveira Joselina L. M. , Marques-Santos Celi , Rocha Ívina E. S. , Barreto-Filho José A. S. , Salvatori Roberto
Published: March 2007

Context: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype.

Methods: We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25–75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT).

Results: We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups.

Conclusions: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.
Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study
Authors: Cohen Pinchas , Rogol Alan D. , Howard Campbell P. , Bright George M. , Kappelgaard Anne-Marie , Rosenfeld Ron G.
Published: March 2007

Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth.

Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment.

Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height sd score (HT-SDS) −2.64] with low IGF-I levels (mean IGF-I SDS −3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF(low) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF(high) group, n = 68] or to a comparison group of conventional GH dose of 40 μg/kg/d (n = 34).

Setting: The study was conducted in a multicenter, outpatient setting.

Primary Outcome Measure: Change in HT-SDS over 2 yr was measured.

Results: One hundred forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6–9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear growth response (P < 0.001, compared with the other two groups). The IGF(high) arm required higher doses (>2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20–346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level.

Conclusion: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses.
A Structural and in Vitro Characterization of Asoprisnil: A Selective Progesterone Receptor Modulator
Authors: Madauss Kevin P. , Grygielko Eugene T. , Deng Su-Jun , Sulpizio Anthony C. , Stanley Thomas B. , Wu Charlene , Short Steve A. , Thompson Scott K. , Stewart Eugene L. , Laping Nicholas J. , Williams Shawn P. , Bray Jeffrey D.
Published: March 2007

Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus.
Microtubule-targeting-dependent reorganization of filopodia
Authors: Schober Joseph M. , Komarova Yulia A. , Chaga Oleg Y. , Akhmanova Anna , Borisy Gary G.
Published: March 2007

Interaction between the microtubule system and actin cytoskeleton has emerged as a fundamental process required for spatial regulation of cell protrusion and retraction activities. In our current studies, analysis of digital fluorescence images revealed targeting of microtubules to filopodia in B16F1 melanoma cells and fibroblasts. We investigated the functional consequence of targeting on filopodia reorganization and examined mechanisms by which microtubules may be guided to, or interact with, filopodia. Live cell imaging studies show that targeting events in lamellipodia wings temporally correlated with filopodia turning toward the lamellipodium midline and with filopodia merging. Rapid uncoupling of targeting with nocodazole decreased filopodia merging events and increased filopodia density. Total internal reflection fluorescence microscopy identified microtubules near the ventral surface and upward movement of targeted filopodia. The role of adhesion sites and microtubule plus-end proteins in targeting was investigated. Correlation of adhesion sites with microtubule targeting to filopodia was not observed and depletion of microtubule plus-end proteins did not significantly alter targeting frequency. We propose that microtubules target filopodia, independent of focal adhesions and plus-end proteins, causing filopodia movement and microtubules regulate filopodia density in lamellipodia wings through filopodia merging events.
Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger
Authors: Bidla Gawa , Dushay Mitchell S. , Theopold Ulrich
Published: March 2007

The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation.
Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes
Authors: Lipp Jesse J. , Hirota Toru , Poser Ina , Peters Jan-Michael
Published: March 2007

The assembly of mitotic chromosomes is controlled by condensin complexes. In vertebrates, condensin I binds to chromatin in prometaphase, confers rigidity to chromosomes and enables the release of cohesin complexes from chromosome arms, whereas condensin II associates with chromosomes in prophase and promotes their condensation. Both complexes are essential for chromosome segregation in anaphase. Although the association of condensins with chromatin is important for the assembly and segregation of mitotic chromosomes, it is poorly understood how this process is controlled. Here we show that the mitotic kinase Aurora B regulates the association of condensin I, but not the interaction of condensin II with chromatin. Quantitative time-lapse imaging of cells expressing GFP-tagged condensin subunits revealed that Aurora B is required for efficient loading of condensin I onto chromosomes in prometaphase and for maintenance of the complex on chromosomes in later stages of mitosis. The three non-SMC subunits of condensin I are Aurora B substrates in vitro and their mitosis-specific phosphorylation depends on Aurora B in vivo. Our data indicate that Aurora B contributes to chromosome rigidity and segregation by promoting the binding of condensin I to chromatin. We have also addressed how Aurora B might mediate the dissociation of cohesin from chromosome arms.
Decision Making in Committees: Transparency, Reputation, and Voting Rules
Authors: Levy Gilat
Published: March 2007

In this paper I analyze the effect of transparency on decision making in committees. I focus on committees whose members are motivated by career concerns. The main result is that when the decision-making process is secretive (when individual votes are not revealed to the public), committee members comply with preexisting biases. For example, if the voting rule demands a supermajority to accept a reform, individuals vote more often against reforms. Transparent committees are therefore more likely to accept reforms. I also find that coupled with the right voting rule, a secretive procedure may induce better decisions than a transparent one. (JEL D71, D72)
Urban Evolutions: The Fast, the Slow, and the Still
Authors: Duranton Gilles
Published: March 2007

With the use of French and US data, new and systematic evidence is provided about the rapid location changes of industries across cities (the fast). Cities are also slowly moving up and down the urban hierarchy (the slow), while the size distribution of cities is skewed to the right and very stable (the still). The model proposed here reproduces these three features. Small, innovation-driven shocks lead to the churning of industries across cities. Then, cities slowly grow or decline following net gains or losses of industries. These changes occur within a stable distribution. The quantitative implications of the model are also explored. (JEL R12, R32)
Market Share Dynamics and the “Persistence of Leadership” Debate
Authors: Sutton John
Published: March 2007

A new 45-industry, 23-year, dataset for Japan is used to investigate the duration of industry leadership. A new scaling relationship linking a firm's current market share with the standard deviation of market share changes is reported. This relationship discriminates in a powerful way between rival candidate theoretical models of market share dynamics. It also makes possible a useful simplification in testing a benchmark model of a Markovian kind. Relative to that model, it is found that at least some industries display a “Chandlerian” bias toward longer durations of leadership than would be present in the benchmark model. (JEL D43, L13)
Internet Advertising and the Generalized Second-Price Auction: Selling Billions of Dollars Worth of Keywords
Authors: Edelman Benjamin , Ostrovsky Michael , Schwarz Michael
Published: March 2007

We investigate the “generalized second-price” (GSP) auction, a new mechanism used by search engines to sell online advertising. Although GSP looks similar to the Vickrey-Clarke-Groves (VCG) mechanism, its properties are very different. Unlike the VCG mechanism, GSP generally does not have an equilibrium in dominant strategies, and truth-telling is not an equilibrium of GSP. To analyze the properties of GSP, we describe the generalized English auction that corresponds to GSP and show that it has a unique equilibrium. This is an ex post equilibrium, with the same payoffs to all players as the dominant strategy equilibrium of VCG. (JEL D44, L81, M37)
Credible Sales Mechanisms and Intermediaries
Authors: McAdams David , Schwarz Michael
Published: March 2007

We consider a seller who faces several buyers and lacks access to an institution to credibly close a sale. If buyers anticipate that the seller may negotiate further, they will prefer to wait before making their best and final offers. This in turn induces the seller to bargain at length with buyers, even if doing so is costly. When the seller's cost of soliciting another round of offers is either very large or very small, the seller credibly commits to an auction and experiences negligible bargaining costs. Otherwise, there may be several rounds of increasing offers and significant seller losses. In these situations, an intermediary with a sufficiently valuable reputation and/or weak marginal incentives regarding price can create value by credibly committing to help sell the object without delay. (JEL C78, D44)
The Economic Impacts of Climate Change: Evidence from Agricultural Output and Random Fluctuations in Weather
Authors: Deschênes Olivier , Greenstone Michael
Published: March 2007

This paper measures the economic impact of climate change on US agricultural land by estimating the effect of random year-to-year variation in temperature and precipitation on agricultural profits. The preferred estimates indicate that climate change will increase annual profits by $1.3 billion in 2002 dollars (2002$) or 4 percent. This estimate is robust to numerous specification checks and relatively precise, so large negative or positive effects are unlikely. We also find the hedonic approach—which is the standard in the previous literature—to be unreliable because it produces estimates that are extremely sensitive to seemingly minor choices about control variables, sample, and weighting. (JEL L25, Q12, Q51, Q54)
Simple Cost-Sharing Contracts
Authors: Chu Leon Yang , Sappington David E. M
Published: March 2007

We extend William Rogerson's (2003) intriguing analysis of simple procurement contracts to settings where the supplier's innate production cost is not necessarily distributed uniformly. Although the simple contract that Rogerson analyzes performs remarkably well when the smaller cost realizations are relatively likely, it can perform poorly when the larger cost realizations are relatively likely. We show that in all settings under consideration, a simple pair of contracts – one that involves linear cost sharing and one that involves full cost reimbursement – can always secure more than 73 percent of the gain achieved with a fully optimal contract. (JEL D86)
Conditional Cash Transfers, Public Provision of Private Goods, and Income Redistribution
Authors: Gahvari Firouz , Mattos Enlinson
Published: March 2007

This paper examines the role of cash transfers as a screening device when combined with in-kind transfers. It shows that linking in-kind to cash transfers makes first-best redistribution possible despite the government's inability to tell rich and poor individuals apart. Moreover, the maximal attainable welfare for the poor can be pushed beyond its first-best level by distorting downward the quality of the indivisible good the poor receive relative to the cash value of their net transfers. Using in-kind transfers alone, as in Besley and Coate (1991), leads to a third-best solution. (JEL D31, H23, H41)
Credit Traps and Credit Cycles
Authors: Matsuyama Kiminori
Published: March 2007

We develop a simple macroeconomic model of credit market imperfections with heterogeneous investment projects. The projects differ in productivity, the investment requirement, and the severity of agency problems behind the borrowing constraints. A movement in borrower net worth shifts the composition of the credit between projects with different productivity levels, thereby causing endogenous investment-specific technological change. Furthermore, such endogenous technological change in turn affects borrower net worth. These composition effects could give rise to credit traps, credit collapse, leapfrogging, credit cycles, and growth miracles in the dynamics of the aggregate investment and borrower net worth. (JEL E22, E44, O33)
Modeling the Transition to a New Economy: Lessons from Two Technological Revolutions
Authors: Atkeson Andrew , Kehoe Patrick J
Published: March 2007

Many view the period after the Second Industrial Revolution as a paradigm of a transition to a new economy following a technological revolution, including the Information Technology Revolution. We build a quantitative model of diffusion and growth during transitions to evaluate that view. With a learning process quantified by data on the life cycle of US manufacturing plants, the model accounts for the key features of the transition after the Second Industrial Revolution. But we find that features like those will occur in other transitions only if a large amount of knowledge about old technologies exists before the transition begins. (JEL L60, N61, N62, N71, N72, O33)
The Cross Section of Foreign Currency Risk Premia and Consumption Growth Risk
Authors: Lustig Hanno , Verdelhan Adrien
Published: March 2007

Aggregate consumption growth risk explains why low interest rate currencies do not appreciate as much as the interest rate differential and why high interest rate currencies do not depreciate as much as the interest rate differential. Domestic investors earn negative excess returns on low interest rate currency portfolios and positive excess returns on high interest rate currency portfolios. Because high interest rate currencies depreciate on average when domestic consumption growth is low and low interest rate currencies appreciate under the same conditions, low interest rate currencies provide domestic investors with a hedge against domestic aggregate consumption growth risk. (JEL E21, E43, F31, G11)
Systemic Anticoagulant Prophylaxis for Central Catheter–Associated Venous Thrombosis in Cancer Patients
Authors: Chan Alexandre , Iannucci Andrea , Dager William E
Published: March 2007

Objective:

To review the literature regarding the incidence of thrombosis in cancer patients with central venous catheters (CVCs) and weigh the evidence supporting thromboprophylaxis in this patient population.

Data Sources:

Clinical literature was identified by searching MEDLINE (1966–February 2007) using the key search terms malignancy, cancer, catheters, prophylaxis, thrombosis, and central venous catheters.

Study Selection and Data Extraction:

An evaluation of retrospective and prospective clinical trials that studied the use of systemic anticoagulants (eg, warfarin, heparin, and low-molecular-weight heparin [LMWH]) to prevent thrombosis with CVCs was performed. Different patient populations, including those manifesting with solid tumor or hematologic malignancy and those undergoing hematopoietic stem cell transplant, were evaluated for this review.

Data Synthesis:

Thrombosis associated with CVCs is a common complication in cancer patients. Most CVC thrombosis will occur within 30 days after placement, with a majority within 8 days. The incidence may depend on the type of CVC and location of the catheter tip. Despite recommendations against the use of systemic anticoagulation for prophylaxis against CVC thrombosis, a potential role continues to be explored in selected settings. Several variables are noted between published clinical trials, making any comparisons difficult to determine whether any benefit exists. Generally, the use of mini-dose warfarin, LMWH, or low-dose unfractionated heparin did not consistently reach significance in reporting a reduction in CVC thrombosis.

Conclusions:

Available data do not support the routine use of anticoagulants for thromboprophylaxis to prevent CVC-related thrombosis. However, several inconsistencies can be found in the studies done to date. More studies are needed to identify subsets of cancer patients who are at higher risk of developing CVC thrombosis and may benefit from prophylactic systemic anticoagulation.
Bevacizumab for Neovascular Ocular Diseases
Authors: Lynch Shalini S , Cheng Christine M
Published: March 2007

Objective:

To review the efficacy and safety of off-label use of bevacizumab for neovascular ocular diseases.

Data Sources:

A PubMed (1966–January 2007) search was conducted using the terms human, intravitreal, bevacizumab, macular, and retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina Society, Macula Society, and Association for Research in Vision and Ophthalmology were reviewed.

Study Selection and Data Extraction:

Controlled studies, unpublished reports involving 100 or more subjects, and published reports describing 5 or more subjects were reviewed. Only English-language articles were considered.

Data Synthesis:

Intravitreal bevacizumab has been evaluated in 133 patients in unpublished controlled studies. Over 3500 patients have been evaluated in open-label studies with duration of follow-up ranging from 3 months to 1 year. The most common use was neovascular age-related macular degeneration (AMD). Other conditions studied included diabetic retinopathy, pathological myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein occlusion, or uveitis. Statistically significant improvements in visual acuity, as well as decreases in retinal thickness and the extent of choroidal neovascularization, were noted. Intravitreal bevacizumab was well tolerated over the short term. In a registry compiling adverse experiences of 7113 intravitreal injections, rates of adverse events were less than or equal to 0.21%.

Conclusions:

Uncontrolled studies support a benefit of intravitreal bevacizumab in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of bevacizumab. Patients should discuss the potential risks and benefits of intravitreal bevacizumab and other available therapies with their physicians before receiving treatment. Controlled trials are needed to characterize the safely and efficacy of intravitreal bevacizumab and determine the optimal treatment regimen.
Spike Timing Amplifies the Effect of Electric Fields on Neurons: Implications for Endogenous Field Effects
Authors: Radman Thomas , Su Yuzhuo , An Je Hi , Parra Lucas C. , Bikson Marom
Published: March 2007

Despite compelling phenomenological evidence that small electric fields (<5 mV/mm) can affect brain function, a quantitative and experimentally verified theory is currently lacking. Here we demonstrate a novel mechanism by which the nonlinear properties of single neurons “amplify” the effect of small electric fields: when concurrent to suprathreshold synaptic input, small electric fields can have significant effects on spike timing. For low-frequency fields, our theory predicts a linear dependency of spike timing changes on field strength. For high-frequency fields (relative to the synaptic input), the theory predicts coherent firing, with mean firing phase and coherence each increasing monotonically with field strength. Importantly, in both cases, the effects of fields on spike timing are amplified with decreasing synaptic input slope and increased cell susceptibility (millivolt membrane polarization per field amplitude). We confirmed these predictions experimentally using CA1 hippocampal neuronsin vitroexposed to static (direct current) and oscillating (alternating current) uniform electric fields. In addition, we develop a robust method to quantify cell susceptibility using spike timing. Our results provide a precise mechanism for a functional role of endogenous field oscillations (e.g., gamma) in brain function and introduce a framework for considering the effects of environmental fields and design of low-intensity therapeutic neurostimulation technologies.
NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death BothIn VitroandIn Vivo
Authors: Liu Yitao , Wong Tak Pan , Aarts Michelle , Rooyakkers Amanda , Liu Lidong , Lai Ted Weita , Wu Dong Chuan , Lu Jie , Tymianski Michael , Craig Ann Marie , Wang Yu Tian
Published: March 2007

Well-documented experimental evidence from bothin vitroandin vivomodels of stroke strongly supports the critical involvement of NMDA receptor-mediated excitotoxicity in neuronal damage after stroke. Despite this, the results of clinical trials testing NMDA receptor antagonists as neuroprotectants after stroke and brain trauma have been discouraging. Here, we report that in mature cortical cultures, activation of either synaptic or extrasynaptic NR2B-containing NMDA receptors results in excitotoxicity, increasing neuronal apoptosis. In contrast, activation of either synaptic or extrasynaptic NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action against both NMDA receptor-mediated and non-NMDA receptor-mediated neuronal damage. A similar opposing action of NR2B and NR2A in mediating cell death and cell survival was also observed in anin vivorat model of focal ischemic stroke. Moreover, we found that blocking NR2B-mediated cell death was effective in reducing infarct volume only when the receptor antagonist was given before the onset of stroke and not 4.5 h after stroke. In great contrast, activation of NR2A-mediated cell survival signaling with administration of either glycine alone or in the presence of NR2B antagonist significantly attenuated ischemic brain damage even when delivered 4.5 h after stroke onset. Together, the present work provides a molecular basis for the dual roles of NMDA receptors in promoting neuronal survival and mediating neuronal damage and suggests that selective enhancement of NR2A-containing NMDA receptor activation with glycine may constitute a promising therapy for stroke.
Conditional Neuronal Simian Virus 40 T Antigen Expression Induces Alzheimer-Like Tau and Amyloid Pathology in Mice
Authors: Park Kevin H. J. , Hallows Janice L. , Chakrabarty Paramita , Davies Peter , Vincent Inez
Published: March 2007

A large body of evidence has shown the activation of a cohort of cell cycle regulators and the duplication of DNA in degenerating neurons of Alzheimer's disease (AD) brain. Activation of these regulators and duplication of chromosomes precede neurodegeneration and formation of neurofibrillary tangles (NFTs), one of the diagnostic lesions of AD. These findings, in combination with evidence for cell cycle regulation of amyloid precursor protein and tau, has led to the hypothesis that reentry into the cell cycle underlies AD pathogenesis. To test this hypothesis directly, we have created transgenic mice with forced cell cycle activation in postmitotic neurons via conditional expression of the simian virus 40 large T antigen (TAg) oncogene. We show that TAg mice recapitulate the cell cycle changes seen in AD and display a neurodegenerative phenotype accompanied by tau pathology and NFT-like profiles. Moreover, plaque-like amyloid deposits, similar to those seen in AD, are also observed in the brains of TAg mice. These data provide support for an essential role of ectopic cell cycle activation in the generation of the characteristic pathological hallmarks of AD. Furthermore, our TAg mice are the first model to develop NFTs and amyloid pathology simultaneously and in the absence of any human transgenes. These mice will be useful for further defining the nongenetic mechanisms in AD pathogenesis and for the development of cell cycle-based therapies for AD.
Dopamine D1/D5Receptor Activation Reverses NMDA Receptor-Dependent Long-Term Depression in Rat Hippocampus
Authors: Mockett Bruce G. , Guévremont Diane , Williams Joanna M. , Abraham Wickliffe C.
Published: March 2007

Activation of dopamine D1/D5receptors (D1/D5Rs) in area CA1 of the rat hippocampus modulates the expression of synaptic plasticity in a manner that is dependent on the timing of the D1/D5R activation. Here, we measured field EPSPs in rat hippocampal slices to examine the modulation of long-term depression (LTD) in CA1 by D1/D5Rs when activated immediately after the induction of LTD by low-frequency stimulation (LFS) or bath application of NMDA or the metabotropic glutamate receptor agonist DHPG [(RS)-3,5-dihydroxyphenylglycine]. Activation of D1/D5Rs by SKF 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide] completely reversed a moderate LFS-induced LTD in a time-dependent manner, presumably through an adenylate cyclase/cAMP cascade. In support of this, general adenylate cyclase activation by forskolin ([3R-(3α,4aβ,5β,6β,6aα,10α,10aβ,10bα)]-5-(acetyloxy)-3-ethenyldodecahydro-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamenthyl-1H-naphtho[2,1-b]pyran-1-one) immediately, but not 60 min, after LFS also reversed the LTD. β-Adrenergic receptor activation by isoproterenol failed to reverse the LTD, indicating that reversal is specific to D1/D5R-mediated increased cAMP production. SKF 38393 only partially reversed a more robust LFS-induced LTD, indicating that some components of consolidated LTD are resistant to reversal. LTD induced by bath application of NMDA, but not DHPG, was also reversed by SKF 38393. Western blot analysis of postsynaptic density fractions after NMDA-induced LTD revealed that the LTD was attributable to dephosphorylation of the AMPA receptor subunit glutamate receptor 1 (GluR1) at serine 845, without a change in total GluR content. Reversal of the LTD by SKF 38393 was associated with rephosphorylation of this same residue. Together, these findings demonstrate a new role for dopamine in the neuromodulation of hippocampal LTD.
Differential Regulation of the Serotonin Transporter Gene by Lithium Is Mediated by Transcription Factors, CCCTC Binding Protein and Y-Box Binding Protein 1, through the Polymorphic Intron 2 Variable Number Tandem Repeat
Authors: Roberts Julian , Scott Alison C. , Howard Mark R. , Breen Gerome , Bubb Vivien J. , Klenova Elena , Quinn John P.
Published: March 2007

The serotoninergic pathways are possible targets for the action of lithium, a therapeutic agent for treatment of bipolar affective disorders. This study aimed to investigate the molecular mechanisms regulating human serotonin transporter gene (SLC6A4) expression by lithium and, specifically, the role of the variable number tandem repeat (VNTR) polymorphic region in intron 2, which is potentially a predisposing genetic factor for bipolar affective disorders. We demonstrated that addition of lithium to human JAr cells led to changes in the levels of SLC6A4 mRNA and protein. Additional investigations revealed that the intron 2 VNTR domain was a potential target for mediation of a transcriptional response to lithium. Properties of two transcription factors, CCCTC binding protein (CTCF) and Y-box binding protein 1 (YB-1), previously shown to be involved in the regulation of SLC6A4 VNTR, were found to be modulated by LiCl. Thus, levels of CTCF and YB-1 mRNA and protein were alteredin vivoin response to LiCl. Furthermore, CTCF and YB-1 showed differential binding to the polymorphic alleles of the VNTR on exposure to LiCl. Our data suggest a model in which differential binding of CTCF and YB-1 to the allelic variants of the intron 2 VNTR can be regulated by lithium and in part result in differential and even aberrant expression of SLC6A4. Our study of the regulation of the SLC6A4 VNTR by lithium may improve the understanding of psychiatric disorders and enable the development of novel therapies for conditions such as bipolar affective disorder to target only the at-risk allele.