bluuebunny/crossref_metadata_2025 huggingface dataset:
Viewpoint and construction grammar: The case of past + now
Authors: Nikiforidou Kiki
Published: August 2010

The combination of a past tense verb with a proximal deictic has been identified in the literature as one of the formal markings of free indirect style (Adamson, 1995). In this article, I examine corpus-derived, non-literary occurrences of the pattern, arguing that construction grammar can provide an adequate, all-encompassing framework for both literary and non-literary uses. Defined as conventional pairings of meaning and form, constructions can accommodate all kinds of semantic, pragmatic, discoursal and textual information as part of their meaning. In the case of the past + now pattern such specifications include a particular discourse or text type, namely narrative, which is the licensing context, and whose conventional association with the particular form constitutes precisely a distinct (discourse) construction. Within this constructional context, the past tense makes a predictable, compositional contribution while the present deictic suppresses part of its meaning signalling instead an anchoring to the current experience, thought, perception of the other. Where present, the progressive aspect enhances further this shift in perspective in a way fully consistent with its basic (non-truth conditional, cognitively defined) semantics. I attempt to show that a constructional approach to past + now may therefore pinpoint the source of the viewpoint effect associated with the pattern in all its uses, and illuminate the relationship of free indirect style with constructions of non-literary discourse.
Creating Bridges Between Researchers and Long-Term Care Homes to Promote Quality of Life for Residents
Authors: Kaasalainen Sharon , Williams Jaime , Hadjistavropoulos Thomas , Thorpe Lilian , Whiting Susan , Neville Susan , Tremeer Juanita
Published: August 2010

Improving the quality of life for long-term care (LTC) residents is of vital importance. Researchers need to involve LTC staff in planning and implementing interventions to maximize the likelihood of success. The purposes of this study were to (a) identify barriers and facilitators of LTC homes’ readiness to implement evidence-based interventions, and (b) develop strategies to facilitate their implementation. A mixed methods design was used, primarily driven by the qualitative method and supplemented by two smaller, embedded quantitative components. Data were collected from health care providers and administrators using 13 focus groups, 26 interviews, and two surveys. Findings revealed that participants appreciated being involved at early stages of the project, but receptiveness to implementing innovations was influenced by study characteristics and demands within their respective practice environment. Engaging staff at the planning stage facilitated effective communication and helped strategize implementation within the constraints of the system.
Maternal Predictors of Behavioral Problems Among Mexican Migrant Farmworker Children
Authors: Siantz Mary Lou de Leon , Coronado Nora , Dovydaitis Tiffany
Published: August 2010

This study investigated the impact of maternal parenting factors on the emotional and behavioral health of Mexican Migrant Head Start children. Although the majority of children sampled in this study did not exhibit problematic behaviors, the findings concluded that children who demonstrated emotional and behavioral problems experienced a more rejecting maternal parenting style, greater parenting stress, and mothers reporting feelings of depression. Gender differences were found between the behavioral and emotional problems of sons and daughters. Surprisingly, years in the United States, maternal birthplace, income, education, and language spoken in the home were not associated with child behavioral problems.
Biomechanical comparisons of four-strand tendon repairs with double-stranded sutures: effects of different locks and suture geometry
Authors: Wu Y. F. , Cao Y. , Zhou Y. L. , Tang J. B.
Published: August 2010

Multi-strand repairs are often used in flexor tendon surgery. We evaluated the strength of four four-strand tendon repairs with different locks and suture geometry. Forty-eight pig flexor tendons were repaired with the following methods: a cross-lock four-strand repair; a U-shaped repair with circle-locks; a modified Kessler repair with Pennington locks (with longitudinal sutures located more centrally; and another modified Kessler (with longitudinal sutures located more laterally). The tendons were loaded to complete failure of the repairs. The two Kessler repairs showed a 35% lower 2 mm gap force, and 15% lower ultimate strength compared with the other two repairs; the differences were of statistical significance. The failure pattern was breakage of sutures in almost all tendons. These four-strand repairs differed in gapping and ultimate strengths. The Kessler-type repairs with different geometry in the longitudinal sutures produced identical strengths. The Kessler-type repairs with Pennington locks were weaker than the two repairs with either cross-locks or circle-locks.
Morphology, size distribution, and aggregate structure of lipopolysaccharide and lipid A dispersions from enterobacterial origin
Authors: Richter Walter , Vogel Vitali , Howe Jörg , Steiniger Frank , Brauser Annemarie , Koch Michel HJ , Roessle Manfred , Gutsmann Thomas , Garidel Patrick , Mäntele Werner , Brandenburg Klaus
Published: August 2010

Lipopolysaccharides (LPSs) from Gram-negative bacteria are strong elicitors of the human immune systems. There is strong evidence that aggregates and not monomers of LPS play a decisive role at least in the initial stages of cell activation of immune cells such as mononuclear cells. In previous reports, it was shown that the biologically most active part of enterobacterial LPS, hexa-acyl bisphosphorylated lipid A, adopts a particular supramolecular conformation, a cubic aggregate structure. However, little is known about the size and morphology of these aggregates, regarding the fact that LPS may have strong variations in the length of the saccharide chains (various rough mutant and smooth-form LPS). Thus, in the present paper, several techniques for the determination of details of the aggregate morphology such as freeze-fracture and cryo-electron microscopy, analytical ultracentrifugation, laser backscattering analysis, and small-angle X-ray scattering were applied for various endotoxin (lipid A and different LPS) preparations. The data show a variety of different morphologies not only for different endotoxins but also when comparing different applied techniques. The data are interpreted with respect to the suitability of the single techniques, in particular on the basis of available literature data.
Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human adipocytes
Authors: Radimerski Tanja M , Grisouard Jean , Timper Katharina , Zulewski Henryk , Christ-Crain Mirjam , Keller Ulrich , Müller Beat
Published: August 2010

Severe systemic infections induce ubiquitous calcitonin (CALC) gene expression with release of calcitonin peptides, namely procalcitonin, calcitonin gene-related peptide and adrenomedullin. Using an in vitro model for bacterial infection, we tested the hypothesis that intracellular calcium concentration ([Ca2+]i) is elevated after lipopolysaccharide (LPS) stimulation and is responsible for the LPS-mediated increase in CALC gene expression and protein secretion. In our human adipocyte model, LPS did not show any cytotoxic effects and induced increased CALC-I gene mRNA expression. Additionally, LPS provoked an elevation in [Ca2+]i. The LPS-induced increase in CALC-I gene mRNA was partially blocked with verapamil, an L-type calcium channel blocker and blocked almost completely with 2-aminoethoxydiphenyl borate, a blocker of store-operated calcium entry and inositol triphosphate-mediated calcium release. Treatment of cells with substances elevating [Ca2+] i led to an increased CALC-I mRNA expression level. The combination of LPS with substances raising [Ca2+]i even potentiated this increase. At the same time, elevated [Ca2+]i attenuated the expression level of the CALC-V gene. These findings indicate that, in human adipocytes, changes in [Ca2+]i are involved in LPSregulated expression of CALC genes, thereby strengthening previous findings postulating a crucial role of intracellular calcium homeostasis in the state of bacterial infection and sepsis.
Temperament influences endotoxin-induced changes in rectal temperature, sickness behavior, and plasma epinephrine concentrations in bulls
Authors: Burdick Nicole C , Carroll Jeffery A , Hulbert Lindsey E , Dailey Jeffery W , Ballou Michael A , Randel Ronald D , Willard Scott T , Vann Rhonda C , Welsh Thomas H
Published: August 2010

This study was designed to determine the influence of temperament on endotoxin-induced changes in body temperature, sickness behavior, and stress hormone concentrations in cattle. Brahman bulls were selected based on temperament score measured 28 d prior to weaning. In dwelling recording devices were used to monitor rectal temperature, and jugular catheters were used to collect blood samples to determine cortisol and epinephrine concentrations before and after LPS administration (0.5 μg/kg body weight). Temperamental bulls had the lowest peak rectal temperature and sickness behavior scores relative to the Calm and Intermediate bulls. Prior to the administration of LPS, Temperamental bulls had greater cortisol and epinephrine concentrations than Calm or Intermediate bulls. Cortisol concentrations increased following LPS administration but were not affected by temperament. Epinephrine concentrations peaked 1 h after LPS administration in Calm bulls. Temperamental bulls did not exhibit an epinephrine response to LPS challenge. These data demonstrate that the temperament of calves can modulate the physiological, behavioral, and endocrine responses of pre-pubertal Brahman bulls to endotoxin challenge. Specifically, temperament differentially affected the rectal temperature, sickness behavior and epinephrine, but not cortisol, responses to LPS challenge.
Hospitality Marketing: A Retrospective Analysis (1960-2010) and Predictions (2010-2020)
Authors: Dev Chekitan S. , Buschman John D. , Bowen John T.
Published: August 2010

Looking at the evolution of marketing as recorded in the pages of the Cornell Hospitality Quarterly , one sees a continual increase in the complexity of the marketing issues for the hospitality industry. Each decade’s articles have been marked by an emphasis on a particular aspect of marketing, generally representing the leading edge of marketing research and thinking. The 1960s, for instance, was the decade of promotion, with numerous articles explaining how to respond to increased competition with an intentional marketing program. The 1970s saw the development of new lodging products and the beginnings of market research, with a greater focus on the customer and on continual product development. The explosion of brands and product tiers in the 1980s ushered in an era of brand management, and the decade also saw the initial lodging industry applications of revenue management, adapted from the airline industry. Following the brutal shakeout of the early 1990s, the lodging industry turned to customer satisfaction and loyalty as key elements of operations, with numerous articles examining ways to measure and manage customer satisfaction. The eruption of the internet dominated the first decade of the twenty-first century, as hospitality companies and guests alike sought to understand how to use this amazing tool. Going forward, the 2010s will continue the changes wrought by electronic media, most particularly the eclipse of printed media and the rise of social media.
Smooth Operating: A Structural Analysis of Social Behavior (SASB) Perspective on Initial Romantic Encounters
Authors: Eastwick Paul W. , Saigal Seema D. , Finkel Eli J.
Published: August 2010

The present report used the comprehensive structural analysis of social behavior (SASB) observational coding scheme to examine which behaviors differentiate smooth from awkward initial romantic encounters. Participants on speed-dates rated as smooth (by independent observers) behaved more warmly and were more other-focused than participants on awkward dates. In addition, participants on smooth dates tended to avoid extremes on the autonomy dimension, exhibiting neither strong independence from nor strong interdependence with their speed-dating partners. Furthermore, the manner in which participants were self-focused (but not other-focused) reliably differentiated smooth from awkward dates; that is, date smoothness strongly predicted how participants reacted to their speed-dating partners (type of self-focus) but only weakly predicted how participants acted toward their speed-dating partners (type of other-focus). Finally, the authors note SASB’s potential to serve as an overarching framework that explains why some interactions go well and others do not.
Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae
Authors: Zaborske John M , Wu Xiaochen , Wek Ronald C , Pan Tao
Published: August 2010

Background

When eukaryotic cells are deprived of amino acids, uncharged tRNAs accumulate and activate the conserved GCN2 protein kinase. Activated Gcn2p up-regulates the general amino acid control pathway through phosphorylation of the translational initiation factor eIF2. In Saccharomyces cerevisiae, Gcn2p is the only kinase that phosphorylates eIF2 to regulate translation through this mechanism. We addressed changes in yeast growth and tRNA aminoacylation, or charging, during amino acid depletion in the presence and absence of GCN2. tRNA charging was measured using a microarray technique which simultaneously measures all cytosolic tRNAs. A fully prototrophic strain, and its isogenic gcn2 Δ counterpart, were used to study depletion for each of the 20 amino acids, with a focus on Trp, Arg, His and Leu, which are metabolically distinct and together provide a good overview on amino acid metabolism.

Results

While the wild-type strain had no observable phenotype upon depletion for any amino acid, the gcn2 Δ strain showed slow growth in media devoid of only Trp or Arg. Consistent with the growth phenotypes, profiles of genome-wide tRNA charging revealed significant decrease in cognate tRNA charging only in the gcn2 Δ strain upon depletion for Trp or Arg. In contrast, there was no change in tRNA charging during His and Leu depletion in either the wild-type or gcn2 Δ strains, consistent with the null effect on growth during loss of these amino acids. We determined that the growth phenotype of Trp depletion is derived from feedback inhibition of aromatic amino acid biosynthesis. By removing Phe and Tyr from the media in addition to Trp, regular growth was restored and tRNATrp charging no longer decreased. The growth phenotype of Arg depletion is derived from unbalanced nitrogen metabolism. By supplementing ornithine upon Arg depletion, both growth and tRNAArg charging were partially restored.

Conclusion

Under mild stress conditions the basal activity of Gcn2p is sufficient to allow for proper adaptation to amino acid depletion. This study highlights the importance of the GCN2 eIF2 kinase pathway for maintaining metabolic homeostasis, contributing to appropriate tRNA charging and growth adaptation in response to culture conditions deficient for the central amino acids, tryptophan and arginine.
Damage of Streptococcus mutans biofilms by carolacton, a secondary metabolite from the myxobacterium Sorangium cellulosum
Authors: Kunze Brigitte , Reck Michael , Dötsch Andreas , Lemme André , Schummer Dietmar , Irschik Herbert , Steinmetz Heinrich , Wagner-Döbler Irene
Published: August 2010

Background

Streptococcus mutans is a major pathogen in human dental caries. One of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. Eradication of such biofilms is extremely difficult. We therefore screened a library of secondary metabolites from myxobacteria for their ability to damage biofilms of S. mutans.

Results

Here we show that carolacton, a secondary metabolite isolated from Sorangium cellulosum, has high antibacterial activity against biofilms of S. mutans. Planktonic growth of bacteria was only slightly impaired and no acute cytotoxicity against mouse fibroblasts could be observed. Carolacton caused death of S. mutans biofilm cells, elongation of cell chains, and changes in cell morphology. At a concentration of 10 nM carolacton, biofilm damage was already at 35% under anaerobic conditions. A knock-out mutant for comD, encoding a histidine kinase specific for the competence stimulating peptide (CSP), was slightly less sensitive to carolacton than the wildtype. Expression of the competence related alternate sigma factor ComX was strongly reduced by carolacton, as determined by a pcomX luciferase reporter strain.

Conclusions

Carolacton possibly interferes with the density dependent signalling systems in S. mutans and may represent a novel approach for the prevention of dental caries.
Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study
Authors: van der Lugt N Margreth , Smits-Wintjens Vivianne EHJ , van Zwieten Paul HT , Walther Frans J
Published: August 2010

Background

Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.

Methods

Retrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.

Results

66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).

Conclusions

Mortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.
A systematic review of evidence for the added benefits to health of exposure to natural environments
Authors: Bowler Diana E , Buyung-Ali Lisette M , Knight Teri M , Pullin Andrew S
Published: August 2010

Background

There is increasing interest in the potential role of the natural environment in human health and well-being. However, the evidence-base for specific and direct health or well-being benefits of activity within natural compared to more synthetic environments has not been systematically assessed.

Methods

We conducted a systematic review to collate and synthesise the findings of studies that compare measurements of health or well-being in natural and synthetic environments. Effect sizes of the differences between environments were calculated and meta-analysis used to synthesise data from studies measuring similar outcomes.

Results

Twenty-five studies met the review inclusion criteria. Most of these studies were crossover or controlled trials that investigated the effects of short-term exposure to each environment during a walk or run. This included 'natural' environments, such as public parks and green university campuses, and synthetic environments, such as indoor and outdoor built environments. The most common outcome measures were scores of different self-reported emotions. Based on these data, a meta-analysis provided some evidence of a positive benefit of a walk or run in a natural environment in comparison to a synthetic environment. There was also some support for greater attention after exposure to a natural environment but not after adjusting effect sizes for pretest differences. Meta-analysis of data on blood pressure and cortisol concentrations found less evidence of a consistent difference between environments across studies.

Conclusions

Overall, the studies are suggestive that natural environments may have direct and positive impacts on well-being, but support the need for investment in further research on this question to understand the general significance for public health.
Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells
Authors: Liu Jing , Hu Ji-liang , Shi Bi-Wei , He Yan , Hu Wei-Xin
Published: August 2010

Background

Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells.

Results

When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.

Conclusions

The TNF-α signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.
The defensive alliance between neutrophils and NK cells as a novel arm of innate immunity
Authors: Costantini Claudio , Cassatella Marco A
Published: August 2010

The immune system is equipped with a plethora of mechanisms that protect the host from the harmful effects of environmental insults. However, the traditional “hierarchical” view of the immune response, in which innate, “nonspecific” cells are first recruited to the site of damage, before the highly “specific”, adaptive immune response develops, has been questioned recently. First, the innate response is much more specific than recognized previously: indeed, each cell of the innate system is not only endowed with an ever-expanding array of germ-line-encoded receptors, which differentiate between distinct insults, but also is modulated continuously by other leukocytes that concomitantly interact with and respond to that particular insult. The other reason is that the cells of the innate system are instrumental for the adaptive system to accomplish its function, as they can also modulate the activity of lymphocytes reciprocally during the entire course of the immune response. This complex pattern of interactions is illustrated by recent advances on the functions of PMNs, clearly showing that unexpectedly, these cells also contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Herein, given the peculiar role of neutrophils and NK cells in inflammation, clearance of pathogens/viral-infected cells, and cancer immunosurveillance, we summarize the current knowledge about the mechanisms whereby neutrophils and NK cells interact and regulate the activities of one another, as well as discuss their potential implications involved in the pathogenesis of chronic, inflammatory pathologies, infections, and tumors.
The C-terminal acidic tail is responsible for the inhibitory effects of HMGB1 on efferocytosis
Authors: Banerjee Sami , Friggeri Arnaud , Liu Gang , Abraham Edward
Published: August 2010

The HMGB1 C-terminal tail is responsible for the in vitro and in vivo inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils.

HMGB1 was described originally as a nuclear protein involved in DNA binding and transcriptional regulation. However, HMGB1 also has an extracellular role as a potent mediator of inflammation and can diminish the uptake of apoptotic cells by phagocytes, a process called efferocytosis. To explore the mechanism responsible for the ability of HMGB1 to inhibit efferocytosis, we examined the role of the C-terminal acidic tail, a region of HMGB1 that has been shown to participate in specific intramolecular interactions. Deletion of the C-terminal tail abrogated the ability of HMGB1 to decrease murine macrophage ingestion of apoptotic neutrophils and to diminish phagocytosis-induced activation of Erk and Rac-1 in macrophages. We found that RAGE plays a major role in efferocytosis, and deletion of the C-terminal tail of HMGB1 prevented binding of HMGB1 to RAGE but not to other macrophage receptors involved in efferocytosis, such as the αVβ3 integrin. Whereas HMGB1 decreased ingestion of apoptotic neutrophils significantly by alveolar macrophages under in vivo conditions in the lungs of mice, this effect was lost when the C-terminal acidic tail was absent from HMGB1. These results demonstrate that the HMGB1 C-terminal tail is responsible for the inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils under in vitro and in vivo conditions.
Evasion of natural killer cells by influenza virus
Authors: Guo Hailong , Kumar Pawan , Malarkannan Subramaniam
Published: August 2010

NK cells are important innate immune effectors during influenza virus infection. However, the influenza virus seems able to use several tactics to counter NK cell recognition for immune evasion. In this review, we will summarize and discuss recent advances regarding the understanding of NK cell evasion mechanisms manipulated by the influenza virus to facilitate its rapid replication inside the respiratory epithelial cells.
Basal body movements orchestrate membrane organelle division and cell morphogenesis inTrypanosoma brucei
Authors: Lacomble Sylvain , Vaughan Sue , Gadelha Catarina , Morphew Mary K. , Shaw Michael K. , McIntosh J. Richard , Gull Keith
Published: August 2010

The defined shape and single-copy organelles of Trypanosoma brucei mean that it provides an excellent model in which to study how duplication and segregation of organelles is interfaced with morphogenesis of overall cell shape and form. The centriole or basal body of eukaryotic cells is often seen to be at the centre of such processes. We have used a combination of electron microscopy and electron tomography techniques to provide a detailed three-dimensional view of duplication of the basal body in trypanosomes. We show that the basal body duplication and maturation cycle exerts an influence on the intimately associated flagellar pocket membrane system that is the portal for secretion and uptake from this cell. At the start of the cell cycle, a probasal body is positioned anterior to the basal body of the existing flagellum. At the G1–S transition, the probasal body matures, elongates and invades the pre-existing flagellar pocket to form the new flagellar axoneme. The new basal body undergoes a spectacular anti-clockwise rotation around the old flagellum, while its short new axoneme is associated with the pre-existing flagellar pocket. This rotation and subsequent posterior movements results in division of the flagellar pocket and ultimately sets parameters for subsequent daughter cell morphogenesis.
Dividend and Corporate Taxation in an Agency Model of the Firm
Authors: Chetty Raj , Saez Emmanuel
Published: August 2010

Recent evidence on the effect of dividend taxes on firm behavior is inconsistent with neoclassical theories of dividend and corporate taxation. We develop a simple agency model in which managers and shareholders have conflicting interests to explain the evidence. In this model, dividend taxation induces managers to undertake unproductive investments by retaining earnings, and creates a first-order deadweight cost. In contrast, corporate taxes do not distort the manager's payout decision and may only create second-order efficiency costs. Corporate income taxation may therefore be a more efficient way to generate revenue than dividend taxation, challenging existing intuitions based on neoclassical models. (JEL D21, G35, H25, H32)
Trade Restrictiveness and Deadweight Losses from US Tariffs
Authors: Irwin Douglas A.
Published: August 2010

This paper calculates a trade restrictiveness index, i.e., the uniform tariff that yields the same welfare loss as an existing tariff structure, for nearly a century of US data. The results show that the average tariff understates the TRI by about 75 percent. The static deadweight loss from US tariffs is about 1 percent of GDP after the Civil War, but falls almost continuously thereafter to less than one-tenth of 1 percent of GDP. Import duties produced an average welfare loss of 40 cents for every dollar of revenue, slightly higher than contemporary estimates of the marginal cost of taxation. (JEL F13, N71, N72)
The General Equilibrium Incidence of Environmental Mandates
Authors: Fullerton Don , Heutel Garth
Published: August 2010

Pollution regulations affect factor demands, relative returns, production, and output prices. In our model, one sector includes pollution as an input that can be a complement or substitute for labor or capital. For each type of mandate, we find conditions where more burden is on labor or on capital. Stricter regulation does not always place less burden on the better substitute for pollution. Also, restrictions on pollution per unit output create an “output-subsidy effect” on factor prices that can reverse the usual output and substitution effects. We find analogous effects for a restriction on pollution per unit capital. (JEL H23, Q53, Q58)
Is Lottery Gambling Addictive?
Authors: Guryan Jonathan , Kearney Melissa S.
Published: August 2010

We present an empirical test for the addictiveness of lottery gambling that exploits an exogenous shock to local market consumption of lottery gambling. It uses the sale of a winning jackpot ticket in a zip code as an instrument for present consumption and tests for a causal relationship between present and future consumption. This test estimates the time path of persistence nonparametrically. Data from the Texas State Lottery suggests that after 6 months, roughly half of the initial increase in lottery consumption is maintained. After 18 months, roughly 40 percent of the initial shock persists, though estimates become less precise. (JEL D12, H27, H71)
Diversification, Diseconomies of Scope, and Vertical Contracting: Evidence from the Taxicab Industry
Authors: Rawley Evan , Simcoe Timothy S.
Published: August 2010

This paper studies how firms reorganize following diversification, proposing that firms use outsourcing, or vertical disintegration, to manage diseconomies of scope. We also consider the origins of scope diseconomies, showing how different underlying mechanisms generate contrasting predictions about the link between within-firm task heterogeneity and the incentive to outsource following diversification. We test these propositions using microdata on taxicab and limousine fleets from the Economic Census. The results show that taxicab firms outsource, by shifting the composition of their fleets toward owner-operator drivers, when they diversify into the limousine business. The magnitude of the shift toward driver ownership is larger in less urban markets, where the tasks performed by taxicab and limousine drivers are more similar. These findings suggest that (1) firms use outsourcing to manage diseconomies of scope at a particular point in the value chain and (2) interagent conflicts can be an important source of scope diseconomies.
Quantitative Relationships between Huntingtin Levels, Polyglutamine Length, Inclusion Body Formation, and Neuronal Death Provide Novel Insight into Huntington's Disease Molecular Pathogenesis
Authors: Miller Jason , Arrasate Montserrat , Shaby Benjamin A. , Mitra Siddhartha , Masliah Eliezer , Finkbeiner Steven
Published: August 2010

An expanded polyglutamine (polyQ) stretch in the protein huntingtin (htt) induces self-aggregation into inclusion bodies (IBs) and causes Huntington's disease (HD). Defining precise relationships between early observable variables and neuronal death at the molecular and cellular levels should improve our understanding of HD pathogenesis. Here, we used an automated microscope that tracks thousands of neurons individually over their entire lifetime to quantify interconnected relationships between early variables, such as htt levels, polyQ length, and IB formation, and neuronal death in a primary striatal model of HD. The resulting model revealed that mutant htt increases the risk of death by tonically interfering with homeostatic coping mechanisms rather than producing accumulated damage to the neuron, htt toxicity is saturable, the rate-limiting steps for inclusion body formation and death can be traced to different conformational changes in monomeric htt, and IB formation reduces the impact of the starting levels of htt of a neuron on its risk of death. Finally, the model that emerges from our quantitative measurements places critical limits on the potential mechanisms by which mutant htt might induce neurodegeneration, which should help direct future research.
Stress-Evoked Tyrosine Phosphorylation of Signal Regulatory Protein α Regulates Behavioral Immobility in the Forced Swim Test
Authors: Ohnishi Hiroshi , Murata Takaaki , Kusakari Shinya , Hayashi Yuriko , Takao Keizo , Maruyama Toshi , Ago Yukio , Koda Ken , Jin Feng-Jie , Okawa Katsuya , Oldenborg Per-Arne , Okazawa Hideki , Murata Yoji , Furuya Nobuhiko , Matsuda Toshio , Miyakawa Tsuyoshi , Matozaki Takashi
Published: August 2010

Severe stress induces changes in neuronal function that are implicated in stress-related disorders such as depression. The molecular mechanisms underlying the response of the brain to stress remain primarily unknown, however. Signal regulatory protein α (SIRPα) is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we show that mice expressing a form of SIRPα that lacks most of the cytoplasmic region manifest prolonged immobility (depression-like behavior) in the forced swim (FS) test. FS stress induced marked tyrosine phosphorylation of SIRPα in the brain of wild-type mice through activation of Src family kinases. The SIRPα ligand CD47 was important for such SIRPα phosphorylation, and CD47-deficient mice also manifested prolonged immobility in the FS test. Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K+-channel subunit Kvβ2 was regulated by SIRPα. Thus, tyrosine phosphorylation of SIRPα is important for regulation of depression-like behavior in the response of the brain to stress.
Centrosome Motility Is Essential for Initial Axon Formation in the Neocortex
Authors: de Anda Froylan Calderon , Meletis Konstantinos , Ge Xuecai , Rei Damien , Tsai Li-Huei
Published: August 2010

The mechanisms underlying the normal development of neuronal morphology remain a fundamental question in neurobiology. Studies in cultured neurons have suggested that the position of the centrosome and the Golgi may predict the site of axon outgrowth. During neuronal migration in the developing cortex, however, the centrosome and Golgi are oriented toward the cortical plate at a time when axons grow toward the ventricular zone. In the current work, we usein situlive imaging to demonstrate that the centrosome and the accompanying polarized cytoplasm exhibit apical translocation in newborn cortical neurons preceding initial axon outgrowth. Disruption of centrosomal activity or downregulation of the centriolar satellite protein PCM-1 affects axon formation. We further show that downregulation of the centrosomal protein Cep120 impairs microtubule organization, resulting in increased centrosome motility. Decreased centrosome motility resulting from microtubule stabilization causes an aberrant centrosomal localization, leading to misplaced axonal outgrowth. Our results reveal the dynamic nature of the centrosome in developing cortical neurons, and implicate centrosome translocation and microtubule organization during the multipolar stage as important determinants of axon formation.
A Novel Transient Glutamatergic Population Migrating from the Pallial–Subpallial Boundary Contributes to Neocortical Development
Authors: Teissier Anne , Griveau Amélie , Vigier Lisa , Piolot Tristan , Borello Ugo , Pierani Alessandra
Published: August 2010

The generation of a precise number of neural cells and the determination of their laminar fate are tightly controlled processes during development of the cerebral cortex. Using genetic tracing in mice, we have identified a population of glutamatergic neurons generated byDbx1-expressing progenitors at the pallial–subpallial boundary predominantly at embryonic day 12.5 (E12.5) and subsequent to Cajal–Retzius cells. We show that these neurons migrate tangentially to populate the cortical plate (CP) at all rostrocaudal and mediolateral levels by E14.5. At birth, they homogeneously populate cortical areas and represent <5% of cortical cells. However, they are distributed into neocortical layers according to their birthdates and express the corresponding markers of glutamatergic differentiation (Tbr1, ER81, Cux2, Ctip2). Notably, this population dies massively by apoptosis at the completion of corticogenesis and represents 50% of dying neurons in the postnatal day 0 cortex. Specific genetic ablation of these transientDbx1-derived CP neurons leads to a 20% decrease in neocortical cell numbers in perinatal animals. Our results show that a previously unidentified transient population of glutamatergic neurons migrates from extraneocortical regions over long distance from their generation site and participates in neocortical radial growth in a non-cell-autonomous manner.
Temporal Discounting of Reward and the Cost of Time in Motor Control
Authors: Shadmehr Reza , Orban de Xivry Jean Jacques , Xu-Wilson Minnan , Shih Ting-Yu
Published: August 2010

Why do movements take a characteristic amount of time, and why do diseases that affect the reward system alter control of movements? Suppose that the purpose of any movement is to position our body in a more rewarding state. People and other animals discount future reward as a hyperbolic function of time. Here, we show that across populations of people and monkeys there is a correlation between discounting of reward and control of movements. We consider saccadic eye movements and hypothesize that duration of a movement is equivalent to a delay of reward. The hyperbolic cost of this delay not only accounts for kinematics of saccades in adults, it also accounts for the faster saccades of children, who temporally discount reward more steeply. Our theory explains why saccade velocities increase when reward is elevated, and why disorders in the encoding of reward, for example in Parkinson's disease and schizophrenia, produce changes in saccade. We show that delay of reward elevates the cost of saccades, reducing velocities. Finally, we consider coordinated movements that include motion of eyes and head and find that their kinematics is also consistent with a hyperbolic, reward-dependent cost of time. Therefore, each voluntary movement carries a cost because its duration delays acquisition of reward. The cost depends on the value that the brain assigns to stimuli, and the rate at which it discounts this value in time. The motor commands that move our eyes reflect this cost of time.
Biochemical and Functional Interaction of Disrupted-in-Schizophrenia 1 and Amyloid Precursor Protein Regulates Neuronal Migration during Mammalian Cortical Development
Authors: Young-Pearse Tracy L. , Suth Seiyam , Luth Eric S. , Sawa Akira , Selkoe Dennis J.
Published: August 2010

Although clinically distinct, schizophrenia and Alzheimer's disease are common and devastating disorders that profoundly impair cognitive function. For Alzheimer's disease, key mechanistic insights have emerged from genetic studies that identified causative mutations in amyloid precursor protein (APP) and presenilin. Several genes have been associated with schizophrenia and other major psychoses, and understanding their normal functions will help elucidate the underlying causes of these disorders. One such gene is disrupted-in-schizophrenia 1 (DISC1). DISC1 and APP have been implicated separately in cortical development, with each having roles in both neuronal migration and neurite outgrowth. Here, we report a previously unrecognized biochemical and functional interaction between DISC1 and APP. Usingin uteroelectroporation in the living rat brain, we show that DISC1 acts downstream of APP and Disabled-1 to regulate cortical precursor cell migration. Specifically, overexpression of DISC1 rescues the migration defect caused by a loss of APP expression. Moreover, knockdown of APP in cultured embryonic neurons results in altered subcellular localization of DISC1. Using transfected cells and normal brain tissue, we show that APP and DISC1 coimmunoprecipitate and that the intracellular domain of APP interacts with the N-terminal domain of DISC1. Based on these findings, we hypothesize that the APP cytoplasmic region transiently interacts with DISC1 to help regulate the translocation of DISC1 to the centrosome, where it plays a key role in controlling neuronal migration during cortical development.
Normal values of serum IGF-1 in adults: results from a Brazilian population
Authors: Rosario Pedro Weslley
Published: August 2010

OBJECTIVE: To determine the normal values of serum IGF-1 (Immulite 2000) in a Brazilian adult (21-70 years) population. SUBJECTS AND METHODS: Healthy volunteers were divided into 10 groups according to age (5-year intervals), with 100 subjects (50 men and 50 women) per group. One-hundred participants were selected for repetition of the test after 12 weeks. RESULTS: No difference in IGF-1 values was observed between men and women, but a progressive reduction of serum IGF-1 with age was seen. The reference values provided by the manufacturer of the assay, although discretely higher, were very close to the values found in this study. A second measurement of IGF-1 after 12 weeks revealed a variation < 20% in 99% of subjects. CONCLUSIONS: This study established the reference range for IGF-1 determined with the Immulite 2000 assay for a large number of healthy Brazilian adults stratified according to age, and suggests that variations > 20% in IGF-1 levels within an interval of 12 weeks cannot be attributed to interassay variability.
Nitrate reductase activity and spad readings in leaf tissues of guinea grass submitted to nitrogen and potassium rates
Authors: Lavres Junior José , Santos Junior João de Deus Gomes dos , Monteiro Francisco Antonio
Published: August 2010

Nitrogen and K deficiency are among the most yield limiting factors in Brazilian pastures. The lack of these nutrients can hamper the chlorophyll biosynthesis and N content in plant tissues. A greenhouse experiment was carried out to evaluate the relationship among N and K concentrations, the indirect determination of chlorophyll content (SPAD readings), nitrate reductase activity (RNO3-) in newly expanded leaf lamina (NL) and the dry matter yield for plant tops of Mombaça grass (Panicum maximum Jacq.). A fractionated 5² factorial design was used, with 13 combinations of N and K rates in the nutrient solution. The experimental units were arranged in a randomized block design, with four replications. Plants were harvested twice. The first harvest occurred 36 days after seedling transplanting and the second 29 days after the first. Significance occurred for the interaction between the N and K rates to SPAD readings and to RNO3- assessment taken on the NL during the first growth. Besides, RNO3- and SPAD readings increased only with the NL N concentration, reaching the highest values of both variables up to about 25 g kg-1, but were ratively constant at higher leaf N. Significant relationships either between SPAD readings or RNO3- activity and shoot dry mass weight were also observed. The critical levels of N concentration in the NL were, respectively, 22 and 17g kg-1 in the first and second harvest. Thus, SPAD instrument and RNO3- assessment can be used as complementary tools to evaluate the N status in forage grass.
Relação solo-relevo-substrato geológico nas restingas da planície costeira do estado de São Paulo
Authors: Coelho Maurício Rizzato , Martins Vanda Moreira , Vidal-Torrado Pablo , Souza Célia Regina de Gouveia , Perez Xosé Luis Otero , Vázquez Felipe Macías
Published: August 2010

Atributos morfológicos de 28 pedons, descritos e amostrados em cronossequências, e datações absolutas por luminescência (TL e LOE) e 14C foram utilizados para elucidar os principais fatores envolvidos na formação e evolução dos Espodossolos nos depósitos marinhos quaternários da planície costeira do Estado de São Paulo. Os solos estudados localizam-se nos municípios de Bertioga (Baixada Santista), Cananeia e Ilha Comprida (Litoral Sul). Essa abordagem, pouco comum nos estudos dos ambientes de planície costeira brasileiros, possibilitou as seguintes interpretações: (a) o relevo, a dinâmica hídrica e o tempo (incluindo as variações do nível relativo do mar) são os principais condicionantes da diferenciação espacial dos Espodossolos nos terraços marinhos; (b) os Espodossolos mais antigos e bem drenados, devido às condições de relevo e rebaixamento do nível do lençol freático, apresentam grande variabilidade e diversidade de seus horizontes e atributos morfológicos, diferindo daqueles mal drenados (antigos ou jovens), em que os horizontes são mais homogêneos; (c) os Espodossolos mais antigos, quando bem drenados, mostram-se em avançado estádio de degradação, enquanto os mal drenados encontram-se bem preservados, indicando que a sua gênese e permanência na paisagem estão ligadas ao relevo, que, por sua vez, controla a dinâmica hídrica; (d) os Espodossolos mais evoluídos e antigos, dotados de horizontes cimentados (orstein), podem ser considerados indicadores pedolitoestratigráficos dos depósitos marinhos pleistocênicos da Formação Cananeia; e (e) a gênese do horizonte orstein se deu em condições topográficas e hidrológicas pretéritas diferentes das atuais, indicando se tratar de solos poligenéticos ou paleossolos.