bluuebunny/crossref_metadata_2025 huggingface dataset:
Culturally and Linguistically Diverse Preschoolers Verbal and Nonverbal Requests
Authors: Saenz Terry Irvine , Iglesias Aquiles , Huer Mary Blake , Parette Howard P.
Published: May 2008

The purpose of this study was to identify the verbal and nonverbal strategies that preschoolers used to obtain objects from peers. Two Head Start classrooms of 41 Puerto Rican and African American preschoolers were observed and videotaped over 1 school year using qualitative methods. The preschoolers used three different strategies to obtain objects from peers during play, including movements toward objects, verbal intentions with movements toward objects, and verbal intentions. The students were able to obtain objects from classmates in 40% of their attempts and were most successful when they combined physical movements toward an object with a request, statement, or claim. The strategies used by the preschoolers and their rates of success varied between the sand, kitchen, and block areas in the two classrooms studied, with children obtaining the greatest success in the block area. The implications of this study's findings for intervention in the classroom by teachers or speech-language pathologists are discussed.
Differences in the Success of NFL Coaches by Race
Authors: Malone Keith D. , Couch Jim F. , Barrett J. Douglas
Published: May 2008

Madden analyzed data on coaching records in the National Football League during the 1990-2002 seasons. The overall conclusion is that African American coaches are held to higher employment standards, with respect to winning, than White coaches. Madden's model used complete seasons coached and omitted partial seasons. Here, the data are analyzed analogously but partial seasons are included. The inclusion of partial season results in a lack of significance of race as a factor in firing. Furthermore, there are other potential explanations of the historically low percentage of African American coaches in the National Football League. These are discussed herein.
The Use of Functional Reading Analysis to Identify Effective Reading Interventions
Authors: Wagner Dana , McComas Jennifer J. , Bollman Kerry , Holton Erin
Published: May 2008

Children who fail to become fluent readers by the end of the primary grades are likely to achieve below same-age peers throughout their school careers. With growing use of curriculum-based measures (CBMs), it is easier to identify those students who are achieving below same-age peers. Moreover, a process of conducting individualized assessment and intervention aimed at improving achievement could be developed within a response to intervention (RTI) model. For example, functional analysis procedures can be used to identify effective reading interventions for students achieving below expectations. The present study employed a multielement design to analyze the effects of various supplemental reading interventions on the oral reading fluency rates of 3 third-grade children. Differential effects were shown across conditions, leading to an individualized intervention recommendation for all participants. Generalized effects were shown over time in CBMs for all participants. Results are discussed in terms of the treatment utility of functional reading analysis for children who exhibit below-expected levels of reading achievement on CMBs and in terms of an RTI approach to identification and service provision for struggling readers.
The Transition Assessment Process and IDEIA 2004
Authors: Sitlington Patricia L. , Clark Gary M.
Published: May 2008

This article will first provide an overview of the transition assessment process in terms of the requirements of the Individuals with Disabilities Education Improvement Act of 2004 and the basic tenets of the process. The second section will provide an overview of the methods of gathering assessment information on the student and on the living, learning, and working environments he or she has identified as part of the transition planning process. The roles of key personnel in the transition assessment process will then be identified. Finally, recommendations will be listed for tying the results of the transition assessment process into the Individualized Education Program, including providing information for the Summary of Performance.
Response to Intervention and Emotional and Behavioral Disorders
Authors: Gresham Frank M.
Published: May 2008

Students with emotional and behavioral difficulties are often unserved or underserved by schools and by mental health systems. One reason for the underidentification of these students is the current and past definitions of emotional disturbance (ED) specified in federal special education legislation (IDEA and IDEIA). These definitions are vague, illogical, and self-contradictory, leading to the wide variability among states in prevalence rates of this disability. The author proposes an alternative approach to defining ED based on response to intervention (RTI). RTI provides the basis for changing, intensifying, and withdrawing interventions for students' emotional and behavioral difficulties. He describess advantages and best practices in using RTI, and provides a discussion of early identification and screening procedures for students who are at risk for ED.
Progress Monitoring in Reading
Authors: Busch Todd W. , Reschly Amy L.
Published: May 2008

In this article, the authors describe the use of curriculum-based measurement (CBM) reading measures within a response-to-intervention (RTI) framework. They examine the characteristics of the measures to illustrate their technical adequacy for use at each tier in an RTI model. Finally, they look at the use of the measures at Tier 3 (special education services) with respect to informing instruction and satisfying the legal requirements of the Individuals with Disabilities Education Improvement Act of 2004.
Assessment and Accommodation Issues Under the No Child Left Behind Act and the Individuals With Disabilities Education Improvement Act
Authors: Shriner James G. , Ganguly Rahul
Published: May 2008

Including students with disabilities in the new standards and accountability systems is one of the key challenges facing school districts around the nation. In this article, the authors first address the evolving assessment and accommodations requirements of both the No Child Left Behind Act of 2001 (NCLB) and the Individuals with Disabilities Education Improvement Act of 2004 (IDEIA), with specific emphasis on the interrelationships between education curriculum standards, participation options, and accommodation decisions. Second, using findings from earlier studies, they discuss the decision-making practices of school personnel with regard to participation and accommodations practices for students with high-incidence disabilities who participate in state assessments with or without accommodations. Finally, they suggest areas for future research, including those that may arise with the emergence of alternate assessments based upon modified achievement standards and from the increased monitoring of accommodation decisions under both NCLB and IDEIA.
Impact of Alternate Assessment on Curricula for Students With Severe Disabilities
Authors: Alisa Lowrey K. , Drasgow Erik , Renzaglia Adelle , Chezan Laura
Published: May 2008

In this article, the authors highlight the impact of alternate assessment on curriculum content for students with severe disabilities. Alternate assessment is a requirement of the Individuals with Disabilities Education Act (IDEA) Ammendments of 1997 and the No Child Left Behind Act (NCLB) of 2001 to ensure that students with the most significant disabilities are included in system accountability measures (Thompson, Lazarus, Clapper, & Thurlow, 2006). The authors review and analyze the purpose and processes of alternate assessment.
Leveling the Digital Playing Field
Authors: Parker David R. , Banerjee Manju
Published: May 2008

As increasing numbers of students with learning disabilities (LD) or attention-deficit/hyperactivity disorder (ADHD) transition to postsecondary education, they encounter a heightened need for proficiency with a wide range of learning technologies. Whereas the Individuals With Disabilities Education Improvement Act of 2004 (IDEIA) requires consideration of a student's assistive technology training needs in high school, the Americans With Disabilities Act does not require any evaluation or training services for postsecondary students with disabilities. In an era of measurable outcomes, it is critical for secondary school personnel to consider effective assessments and relevant interventions when college-bound students with cognitive disabilities lack proficiency with these technologies. Survey research at a highly competitive public university found significant differences between the technology needs, preferences, and fluency of undergraduates with and without disabilities. This article presents findings from that study as well as implications for teachers and evaluators who assist students with LD and ADHD in their transition planning for postsecondary education.
Sputter alloying of Ni, Ti and Hf for fabrication of high temperature shape memory thin films
Authors: Sanjabi S. , Sadrnezhaad S. K. , Barber Z. H.
Published: May 2008

In the present paper, the fabrication and characterisation of typical high temperature Ni(Ti+Hf) alloyed thin films produced by simultaneous sputter deposition from separate elemental Ni, Ti and Hf targets are presented. Film composition, determined by energy dispersive X-ray spectroscopy, was controlled by adjusting the ratio of powers applied to each target. Films deposited at room temperature had an amorphous structure and subsequent annealing at 550°C was carried out in a high vacuum environment, based on crystallisation temperature evaluation by differential scanning calorimetry (DSC). High temperature martensitic transformation, confirmed by DSC and variable temperature X-ray diffraction (XRD), was achieved by deposition of (Ti+Hf) rich Ni–Ti–Hf films. Any slight change of composition towards Ni rich reduced the transformation temperature. Atomic force microscopy and XRD illustrated that the films had a fine grain structure (∼100 nm). One way shape memory effect was observed at ∼200°C in a film with composition of 15·6 at.-%Hf.
Hydroxyapatite coatings on NaOH treated Ti–6Al–4V alloy using sol–gel precursor
Authors: Balakrishnan A. , Lee B. C. , Kim T. N. , Panigrahi B. B.
Published: May 2008

In this study, hydroxyapatite (HA) was coated by sol–gel method on Ti–6Al–4V alloy substrates and on micropolished surface after NaOH treatment. The former shows the cracks and poor bonding of HA whereas the latter shows coating without cracks and higher bonding strength. The higher bonding strength on NaOH treated sample could be attributed to the formation of thin sodium titanium oxide layer, the high surface roughness and high interfacial bonding between HA and substrate.
Study on performance of uncoated and coated tools in milling of Al–4%Cu/B4C metal matrix composites
Authors: Übeyli M. , Karakaş M. S. , Acır A. , Ögel B.
Published: May 2008

This paper studies the performance of uncoated and multiple coated tools in milling of Al–4%Cu/B4Cp metal matrix composites (MMCs). Effect of cutting speed on the wear behaviour of tools and tool wear mechanisms were investigated. The milling operations were carried out at five different cutting speeds (100, 130, 169, 220 and 286 m min−1) by keeping the feedrate constant (0·15 mm z−1). In addition, flank wear limit value, VB=0·3 mm was selected as reference value to determine and compare wear of the tools investigated. After milling experiments, an optical microscope was used to measure the magnitude of flank wear on the tools, whereas scanning electron microscope (SEM) was utilised to examine wear mechanisms. According to experimental results, the multiple coated tool showed better performance than uncoated one at all cutting speeds and flank wear that changed with cutting speeds significantly was found as the main wear mechanism for both tools.
Effect of in situ reaction on microstructure of TIG welding SiCp/A356 with Ti as filler metal
Authors: Coo Y.
Published: May 2008

The effect of in situ reaction on the microstructure of welded joints of aluminium matrix composite SiCp/A356 had been studied. It showed that during tungsten inert gas (TIG) welding, with Ti as filler metal, the properties of welding pool, such as the high viscosity and poor flowability would be improved. As a result, the drawbacks in the TIG welding were prevented distinctly. The typical pernicious interfacial reaction microstructure Al4C3 could be restrained from the interface between aluminium matrix and reinforcement particles. At the same time, owing to in situ reinforcement effect of Ti, the newly formed phase TiC was distributed uniformly in the weld resulted in welding the composite successfully.
Influence of post-weld heat treatment on tensile properties of modified 9Cr–1Mo ferritic steel base metal
Authors: Samuel E. Isaac , Choudhary B. K. , Rao K. Bhanu Sankara
Published: May 2008

The paper presents the influence of post-weld heat treatment (PWHT) on tensile properties of modified 9Cr–1Mo ferritic steel base metal. Tensile tests at room and elevated temperatures (300–873 K) were performed on specimens in normalised and tempered condition as well as with additional PWHT (993 K for 1 h; 1013 K for 1 h and 1033 K for 1 h). The yield and ultimate tensile strengths decrease gradually up to intermediate temperatures followed by a rapid fall at high temperatures in all heat treatment conditions. At intermediate temperatures, the steel exhibited ductility minima, serrated flow, negative strain rate sensitivity on flow stress and peak in the average work hardening rate. The influence of additional PWHT is reflected in a systematic and gradual decrease in both the yield and tensile strength values with increasing PWHT temperature from 993 to 1033 K for 1 h. However, there has been no appreciable change in ductility values as well as the fracture mode in PWHT conditions compared with those observed in normalised and tempered condition. Comparison of strength values in PWHT conditions suggested that the strength values remained higher than the average values specified in the French Nuclear Design Code, RCC-MR.
PET polymer ablation using excimer laser for nozzle plate application
Authors: Pan C.-T. , Yang H. , Wei M.-K. , Chang F.-Y.
Published: May 2008

Polyethylene terephthalate (PET) film drilling using a 248 nm excimer laser through photomask projection is presented. The parameter effects of laser fluence, shot number and repetition rate on the processing results are examined. A high quality microhole array with 50 μm thick PET film is fabricated. When the projection process is carried out, the diameter differences in the microhole in the front and back side of PET are observed. This causes a conical shape in the kerf. The formation of this conical shape in terms of the laser process parameters is discussed. The process parameter effects are investigated and characterised to improve the PET microhole laser machining quality.
Kinetics of rafting in a single crystal superalloy: Effects of residual microsegregation
Authors: Reed R. C. , Cox D. C. , Rae C. M. F.
Published: May 2008

The kinetics of directional γ′ coarsening, known as rafting, are examined in the nickel based single crystal superalloy CMSX-4. Electron microscopy and image analysis are used to characterise heat treated specimens, prestrained in creep to a plastic strain beyond the threshold required to initiate rafting. The kinetics of rafting are found to be sensitive to the presence of microsegregation from casting, incompletely removed by the heat treatment process; thus the dendritic regions raft appreciably faster than the interdendritic ones – this despite rhenium enrichment at the dendrite cores consistent with its preferred partitioning during solidification. Estimates of the activation energy required for rafting in the two regions are established and Avrami-type equations developed. Since the important γ′ forming elements aluminium and tantalum are known to partition interdendritically causing an enhanced γ′ fraction, it is suggested that the correspondingly smaller γ channel width so caused is responsible for the greater resistance to rafting displayed by the interdendritic regions.
Effect of heat treatment on microstructure and mechanical properties of Cr–Ni–Mo–Nb steel
Authors: Wang M. Q. , Dong H. , Hui W. J. , Shi J.
Published: May 2008

The microstructure and mechanical properties of a medium carbon Cr–Ni–Mo–Nb steel in quenched and tempered conditions were investigated using transmission electron microscopy (TEM), X-ray analysis, and tensile and impact tests. Results showed that increasing austenitisation temperature gave rise to an increase in the tensile strength due to more complete dissolution of primary carbides during austenitisation at high temperatures. The austenite grains were fine when the austenitisation temperature was <1373 K owing to the pinning effect of undissolved Nb(C,N) particles. A tensile strength of 1600 MPa was kept at tempering temperatures up to 848 K, while the peak impact toughness was attained at 913 K tempering, as a result of the replacement of coarse Fe rich M3C carbides by fine Mo rich M2C carbides. Austenitisation at 1323 K followed by 913 K tempering could result in a combination of high strength and good toughness for the Cr–Ni–Mo–Nb steel.
Microstructure and properties of carbide free bainite railway wheels produced by programmed quenching
Authors: Zhang M. R. , Gu H. C.
Published: May 2008

A kind of carbide free bainite steel was used to produce railway wheels. The alloy design, manufacture process, microstructure and behaviours are summarised. The novel steel is distinctively superior in excellent combination of strength and toughness compared with the traditional pearlite type wheel steels. The details of the microstructure of novel steel have been investigated in nanoscale.
A novel analytical–artificial neural network model to improve efficiency of high pressure descaling nozzles in hot strip rolling of steels
Authors: Kermanpur A. , Ebnonnasir A. , Hedayati M.
Published: May 2008

Hot strip mills use hydraulic descaling to remove oxide scales from steel strip formed after the reheat furnace and during hot rolling. In the present work, a novel analytical–artificial neural network (AANN) model was developed to improve the efficiency of high pressure (HP) hydraulic descaling operation using flat spray nozzles. The AANN model is able to analytically compute the spray force and depth and to estimate the spray impact using an artificial neural network approach. The combined model was trained based on the industrial data from the hot strip rolling mills of Mobarakeh Steel Complex. The spray angle, spray pressure, vertical spray height and water flowrate were all considered as the main input parameters of the HP descaling operation. The AANN model can predict the spray force, impact and depth under any given descaling condition. A sensitivity analysis was carried out using the combined model. It is shown that, among all process parameters, the spray angle followed by the spray height are the most important parameters affecting the spray impact. The model developed can be used as a proper tool to improve the efficiency of the descaling system in terms of achieving the highest spray impact under any process condition.
Effects of Cr, Mn, Si, Cu and Zr on microstructure and mechanical properties of high carbon Fe–16Al alloy
Authors: Khaple Shivkumar , Baligidad R. G. , Rao S.
Published: May 2008

Effects of alloying elements Cr, Mn, Si, Cu and Zr on the microstructure and mechanical properties of Fe3Al (Fe–16Al) based alloy containing ∼0·5 wt-%C have been investigated. Six alloys were prepared by a combination of air induction melting with flux cover and electroslag refining (ESR). ESR ingots were hot forged and hot rolled at 1373 K and were further characterised with respect to microstructure and mechanical properties. The base alloy and the alloys containing Cr, Mn, Si and Cu exhibit a two phase microstructure of Fe3AlC0·5 precipitates in Fe3Al matrix whereas the alloy containing Zr exhibits a three phase microstructure, the additional phase being Zr rich carbide precipitates. Cr and Mn have high solubility in Fe3AlC0·5 precipitates as compared to Fe3Al matrix whereas Cu and Si have very high solubility in Fe3Al matrix compared to Fe3AlC0·5 precipitate and Zr has very low solubility in both Fe3Al matrix and Fe3AlC0·5 precipitate. No significant improvement in room and high temperature (at 873 K) strengths was observed by addition of these alloying elements. Furthermore, it was observed that addition of these alloying elements has resulted in poor room and high temperature ductility. Addition of Cr, Mn, Si and Cu has resulted in marginal improvement in creep life, whereas Zr improved the creep life significantly from 22·3 to 117 h.
Numerical simulation of spot welding for galvanised sheet steels
Authors: Zhang Y. S. , Xu J. , Lai X. M. , Chen G. L.
Published: May 2008

Galvanised sheet steels are now widely used to be the substrate for body in white (BIW) construction in the automotive industry. Weldability of galvanised sheet steels much worsened compared to spot welding of low carbon steels. The present paper develops a 2D axisymmetric model and employs an incremental coupled thermal–electrical–mechanical analysis to predict the nugget development during resistance spot welding (RSW) of galvanised sheet steels. Temperature dependent contact resistance for faying surfaces was determined to take into account of the influence of zinc coat for spot welding galvanised sheet steels. The effect of dynamic contact radii on temperature distribution was studied and compared with results under constant contact area assumption. The predicted nugget shape and size agreed well with the experimental data. Higher current and longer welding time should be applied for galvanised sheet steels compared to low carbon steel spot welding. The proposed model can be applied to predict weld quality and choose optimal welding conditions for spot welding galvanised sheet steels.
Fuzzy rule based approach for predicting weld bead geometry in gas tungsten arc welding
Authors: Ghanty P. , Paul S. , Roy A. , Mukherjee D. P. , Pal N. R. , Vasudevan M. , Kumar H. , Bhaduri A. K.
Published: May 2008

The use of fuzzy rule based systems to model the relationship between weld control parameters and the weld bead geometry features is explored in this paper. The Takagi–Sugeno model with linear functions of the inputs is used as the rule consequents. Given some training data, the authors use exploratory data analysis to find an initial rule base. The system parameters, e.g. consequent parameters, are estimated using a mixture of least square error (LSE) method and gradient search. The system is tested on three datasets and the performance is found to be satisfactory compared to the multilayer perceptron (MLP) and radial basis function (RBF) neural networks based systems.
Development of autocompleting friction welding method
Authors: Kimura M. , Fujii T. , Utsumi D. , Kusaka M. , Seo K.
Published: May 2008

This paper describes an autocompleting friction welding method that was carried out to weld with an insert piece set between fixed base metals. The base metal was low carbon steel, and the faying surface of the fixed specimen had a 10 mm diameter. The effect of the thickness of the insert piece (insert thickness) on the joining phenomena was investigated. When the insert thickness was 3˙2 mm and the friction welding conditions were a friction speed of 27˙5 s–1 and friction pressure of 36 MPa, the insert piece had a shear fracture toward the circumferential direction in the peripheral portion of the weld interfaces by the initial peak produced during the friction process. The joint also had cracks at the adjacent region of the weld interfaces, although it had the same tensile strength as the base metal. On the other hand, the joint made using the insert piece with a groove on its peripheral portion had the same tensile strength as the base metal, where it fractured. This joint also had 90° bend ductility without cracks. In this case, the optimum insert thickness was 4˙0 mm, and the thickness at the bottom of the grooves (groove bottom thickness) was 1˙2 mm with an 11 mm inner groove diameter, and the friction welding conditions were a friction speed of 27˙5 s–1 and friction pressure of 36 MPa. In conclusion, a sound friction welded joint was made by an autocompleting friction welding method.
Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma
Authors: Hidaka Tomonori , Nakahata Shingo , Hatakeyama Kinta , Hamasaki Makoto , Yamashita Kiyoshi , Kohno Takashi , Arai Yasuhito , Taki Tomohiko , Nishida Kazuhiro , Okayama Akihiko , Asada Yujiro , Yamaguchi Ryoji , Tsubouchi Hirohito , Yokota Jun , Taniwaki Masafumi , Higashi Yujiro , Morishita Kazuhiro
Published: May 2008

Adult T-cell leukemia/lymphoma (ATLL) is caused by latent human T-lymphotropic virus-1 (HTLV-1) infection. To clarify the molecular mechanism underlying leukemogenesis after viral infection, we precisely mapped 605 chromosomal breakpoints in 61 ATLL cases by spectral karyotyping and identified frequent chromosomal breakpoints in 10p11, 14q11, and 14q32. Single nucleotide polymorphism (SNP) array–comparative genomic hybridization (CGH), genetic, and expression analyses of the genes mapped within a common breakpoint cluster region in 10p11.2 revealed that in ATLL cells, transcription factor 8 (TCF8) was frequently disrupted by several mechanisms, including mainly epigenetic dysregulation. TCF8 mutant mice frequently developed invasive CD4+ T-cell lymphomas in the thymus or in ascitic fluid in vivo. Down-regulation of TCF8 expression in ATLL cells in vitro was associated with resistance to transforming growth factor β1 (TGF-β1), a well-known characteristic of ATLL cells, suggesting that escape from TGF-β1–mediated growth inhibition is important in the pathogenesis of ATLL. These findings indicate that TCF8 has a tumor suppressor role in ATLL.
Comparison of generalized estimating equations and quadratic inference functions using data from the National Longitudinal Survey of Children and Youth (NLSCY) database
Authors: Odueyungbo Adefowope , Browne Dillon , Akhtar-Danesh Noori , Thabane Lehana
Published: May 2008

Background

The generalized estimating equations (GEE) technique is often used in longitudinal data modeling, where investigators are interested in population-averaged effects of covariates on responses of interest. GEE involves specifying a model relating covariates to outcomes and a plausible correlation structure between responses at different time periods. While GEE parameter estimates are consistent irrespective of the true underlying correlation structure, the method has some limitations that include challenges with model selection due to lack of absolute goodness-of-fit tests to aid comparisons among several plausible models. The quadratic inference functions (QIF) method extends the capabilities of GEE, while also addressing some GEE limitations.

Methods

We conducted a comparative study between GEE and QIF via an illustrative example, using data from the "National Longitudinal Survey of Children and Youth (NLSCY)" database. The NLSCY dataset consists of long-term, population based survey data collected since 1994, and is designed to evaluate the determinants of developmental outcomes in Canadian children. We modeled the relationship between hyperactivity-inattention and gender, age, family functioning, maternal depression symptoms, household income adequacy, maternal immigration status and maternal educational level using GEE and QIF. Basis for comparison include: (1) ease of model selection; (2) sensitivity of results to different working correlation matrices; and (3) efficiency of parameter estimates.

Results

The sample included 795, 858 respondents (50.3% male; 12% immigrant; 6% from dysfunctional families). QIF analysis reveals that gender (male) (odds ratio [OR] = 1.73; 95% confidence interval [CI] = 1.10 to 2.71), family dysfunctional (OR = 2.84, 95% CI of 1.58 to 5.11), and maternal depression (OR = 2.49, 95% CI of 1.60 to 2.60) are significantly associated with higher odds of hyperactivity-inattention. The results remained robust under GEE modeling. Model selection was facilitated in QIF using a goodness-of-fit statistic. Overall, estimates from QIF were more efficient than those from GEE using AR (1) and Exchangeable working correlation matrices (Relative efficiency = 1.1117; 1.3082 respectively).

Conclusion

QIF is useful for model selection and provides more efficient parameter estimates than GEE. QIF can help investigators obtain more reliable results when used in conjunction with GEE.
The brown adipocyte differentiation pathway in birds: An evolutionary road not taken
Authors: Mezentseva Nadejda V , Kumaratilake Jaliya S , Newman Stuart A
Published: May 2008

Background

Thermogenic brown adipose tissue has never been described in birds or other non-mammalian vertebrates. Brown adipocytes in mammals are distinguished from the more common white fat adipocytes by having numerous small lipid droplets rather than a single large one, elevated numbers of mitochondria, and mitochondrial expression of the nuclear gene UCP1, the uncoupler of oxidative phosphorylation responsible for non-shivering thermogenesis.

Results

We have identified in vitro inductive conditions in which mesenchymal cells isolated from the embryonic chicken limb bud differentiate into avian brown adipocyte-like cells (ABALCs) with the morphological and many of the biochemical properties of terminally differentiated brown adipocytes. Avian, and as we show here, lizard species lack the gene for UCP1, although it is present in amphibian and fish species. While ABALCs are therefore not functional brown adipocytes, they are generated by a developmental pathway virtually identical to brown fat differentiation in mammals: both the common adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ), and a coactivator of that factor specific to brown fat differentiation in mammals, PGC1α, are elevated in expression, as are mitochondrial volume and DNA. Furthermore, ABALCs induction resulted in strong transcription from a transfected mouse UCP1 promoter.

Conclusion

These findings strongly suggest that the brown fat differentiation pathway evolved in a common ancestor of birds and mammals and its thermogenicity was lost in the avian lineage, with the degradation of UCP1, after it separated from the mammalian lineage. Since this event occurred no later than the saurian ancestor of birds and lizards, an implication of this is that dinosaurs had neither UCP1 nor canonically thermogenic brown fat.
Association of single-nucleotide polymorphisms in RHOB and TXNDC3 with knee osteoarthritis susceptibility: two case-control studies in East Asian populations and a meta-analysis
Authors: Shi Dongquan , Nakamura Takahiro , Nakajima Masahiro , Dai Jin , Qin Jianghui , Ni Haijian , Xu Yong , Yao Chen , Wei Jia , Liu Baorui , Ikegawa Shiro , Jiang Qing
Published: May 2008

Introduction

Conflicting findings on the association of single nucleotide polymorphisms (SNPs) in RHOB and TXNDC3 with susceptibility to knee osteoarthritis (OA) have been reported in European Caucasians. To examine the associations of these SNPs with OA in East Asian populations and to evaluate their global significance, we conducted two case-control studies in 955 Chinese and 750 Japanese patients.

Methods

We genotyped the previously implicated SNPs rs585017 (in RHOB) and rs4720262 (in TXNDC3) in patients with primary symptomatic knee OA with radiographic confirmation and in matched control individuals, and analyzed their associations. We further conducted a meta-analysis of the study findings together with those of previously reported European studies using the DerSimonian-Laird procedure.

Results

A significant association of RHOB with knee OA was observed in male Chinese patients (P = 0.02). No significant associations were found for RHOB in any other comparisons in the East Asian populations. The association of TXNDC3 was replicated in Chinese female (P = 0.04) and Japanese (P = 0.03) patients, although none of these associations persisted after Bonferroni correction. Significant association (P = 0.02 for the allelic frequency) with nonsignificant heterogeneity was found in the East Asian replication study. No significant association was found in any comparison in the meta-analysis for all studies.

Conclusion

Our study replicates the association, previously reported in European Caucasians, of TXNDC3 with knee OA susceptibility in an East Asian population.
Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53
+/-mice
Authors: Dunphy Karen A , Blackburn Anneke C , Yan Haoheng , O'Connell Lauren R , Jerry D Joseph
Published: May 2008

Introduction

Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome.

Methods

Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues.

Results

Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors.

Conclusion

Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.
Multiple Systems in Decision Making
Authors: Sanfey Alan G. , Chang Luke J.
Published: May 2008

Neuroeconomics seeks to gain a greater understanding of decision making by combining theoretical and methodological principles from the fields of psychology, economics, and neuroscience. Initial studies using this multidisciplinary approach have found evidence suggesting that the brain may be employing multiple levels of processing when making decisions, and this notion is consistent with dual‐processing theories that have received extensive theoretical consideration in the field of cognitive psychology, with these theories arguing for the dissociation between automatic and controlled components of processing. While behavioral studies provide compelling support for the distinction between automatic and controlled processing in judgment and decision making, less is known if these components have a corresponding neural substrate, with some researchers arguing that there is no evidence suggesting a distinct neural basis. This chapter will discuss the behavioral evidence supporting the dissociation between automatic and controlled processing in decision making and review recent literature suggesting potential neural systems that may underlie these processes.
Maternal Thyroid Hormone: A Strong Repressor of Neuronal Nitric Oxide Synthase in Rat Embryonic Neocortex
Authors: Sinha Rohit Anthony , Pathak Amrita , Mohan Vishwa , Bandyopadhyay Sanghamitra , Rastogi Leena , Godbole Madan M.
Published: May 2008

Understanding of how maternal thyroid inadequacy during early gestation poses a risk for developmental outcomes is still a challenge for the neuroendocrine community. Early neocortical neurogenesis is accompanied by maternal thyroid hormone (TH) transfer to fetal brain, appearance of TH receptors, and absence of antineurogenesis signals, followed by optimization of neuronal numbers through apoptosis. However, the effects of TH deprivation on neurogenesis and neuronal cell death before the onset of fetal thyroid are still not clear. We show that maternal TH deficiency during early gestational period causes massive premature elevation in the expression of neuronal nitric oxide synthase (nNOS) with an associated neuronal death in embryonic rat neocortex. Maternal hypothyroidism was induced by feeding methimazole (0.025% wt/vol) in the drinking water to pregnant Sprague Dawley rats from embryonic d 6. Cerebral cortices from fetuses were harvested at different embryonic stages (embryonic d 14, 16, and 18) of hypothyroid and euthyroid groups. Immunoblotting and real-time PCR results showed that both protein and RNA levels of nNOS were prematurely increased under maternal hypothyroidism, and showed reversibility upon T4 administration. Immunohistochemistry revealed an increased nNOS immunoreactivity in both the cortical plate and proliferative zone of neocortex along with a corroborative decrease in the microtubule associated protein-2 positive neurons under maternal TH insufficiency. Results combined, put forth nNOS as a novel target of maternal TH action in embryonic neocortex, and underscore the importance of prenatal screening and timely rectification of maternal TH insufficiency, even of a moderate degree.
The G Protein-Coupled Receptor GPR30 Inhibits Human Urothelial Cell Proliferation
Authors: Teng Jian , Wang Zun-Yi , Prossnitz Eric R. , Bjorling Dale E.
Published: May 2008

We have previously shown that estrogen stimulates cell proliferation in both normal and transformed urothelial cells mainly through activation of the two primary estrogen receptors (ERs), ERα and ERβ. A growing body of evidence suggests that estrogen also initiates nongenomic effects that cannot be explained by activation of primary ERs. In the present study, we observed that urothelial cells express high amounts of GPR30, a G protein-coupled receptor recently identified as a candidate for membrane-associated estrogen binding. Membrane- impermeable bovine serum albumin-conjugated 17β-estradiol and the specific GPR30 agonist G-1 both inhibited urothelial cell proliferation in a concentration-dependent manner. Transient overexpression of GPR30 inhibited 17β-estradiol (E2)-induced cell proliferation. Decreased GPR30 expression caused by specific small interfering RNA increased E2-induced cell proliferation. These results indicate that membrane-associated inhibitory effects of E2 on cell proliferation correlate with abundance of GPR30. Although E2 induced a significant increase in caspase-3/7 activity, G-1 did not, suggesting that the GPR30-mediated inhibitory effect on cell proliferation was not caused by apoptosis. Furthermore, we found that G-1 failed to induce c-fos, c-jun, and cyclin D1 expression, and GPR30 overexpression abolished E2-induced c-fos, c-jun, and cyclin D1 expression. However, inactivation of GPR30 by small interfering RNA increased c-fos, c-jun, and cyclin D1 expression. These results suggest that GPR30-mediated inhibition of urothelial cell proliferation is the result of decreased cyclin D1 by down-regulation of activation protein-1 signaling.
Estrogen Receptor α Signaling Pathways Differentially Regulate Gonadotropin Subunit Gene Expression and Serum Follicle-Stimulating Hormone in the Female Mouse
Authors: Glidewell-Kenney C. , Weiss J. , Hurley L. A. , Levine J. E. , Jameson J. L.
Published: May 2008

Estrogen, acting via estrogen receptor (ER)α, regulates serum gonadotropin levels and pituitary gonadotropin subunit expression. However, the cellular pathways mediating this regulation are unknown. ERα signals through classical estrogen response element (ERE)-dependent genomic as well as nonclassical ERE-independent genomic and nongenomic pathways. Using targeted mutagenesis in mice to disrupt ERα DNA binding activity, we previously demonstrated that ERE-independent signaling is sufficient to suppress serum LH levels. In this study, we examined the relative roles of ERE-dependent and -independent estrogen signaling in estrogen regulation of LH, FSH, prolactin, and activin/inhibin subunit gene expression, pituitary LH and FSH protein content, and serum FSH levels. ERE-independent signaling was not sufficient for estrogen to induce pituitary prolactin mRNA or suppress pituitary LHβ mRNA, LH content, or serum FSH in estrogen-treated ovariectomized mice. However, ERE-independent signaling was sufficient to reduce pituitary glycoprotein hormone α-subunit, FSHβ, and activin-βB mRNA expression. Together with previous serum LH results, these findings suggest ERE-independent ERα signaling suppresses serum LH via reduced secretion, not synthesis. Additionally, ERE-dependent and ERE-independent ERα pathways may distinctly regulate steps involved in the synthesis and secretion of FSH.
The Anabolic Response to Parathyroid Hormone Is Augmented in Rac2 Knockout Mice
Authors: Kawano Tsutomu , Troiano Nancy , Adams Douglas J. , Jun Wu Jian , Sun Ben-hua , Insogna Karl
Published: May 2008

PTH is the only currently available anabolic therapy for osteoporosis. In clinical practice, the skeletal response to PTH varies and because therapy is limited to 2 yr, approaches to maximize the therapeutic response are desirable. Rac2 is a small GTPase that is expressed only in hematopoietic tissue. Rac2−/− mice have a slight increase in bone mass and osteoclasts isolated from these animals have reduced basal resorptive activity and reduced chemotaxis. To evaluate the anabolic response to PTH in Rac2−/− mice, we treated 18 Rac2−/− and 17 control, age-matched wild-type animals once daily for 28 d with 80 ng/g body weight of h(1–34)PTH. Treatment resulted in significantly greater increments in spinal, femur, and total bone density in the Rac2−/− as compared with wild-type animals. Microcomputed tomography analysis demonstrated greater increases in trabecular thickness and cortical thickness in the knockout mice. Interestingly, histomorphometric analysis showed an equivalent increase in osteoblast and osteoclast number in response to PTH treatment in both groups of animals. However, as judged by changes in serum markers, the resorptive response to PTH was impaired. Thus, telopeptide of type 1 collagen was 15.9 ± 6.9 ng/ml after PTH treatment in the knockout animals and 26.8 ± 11.1 ng/ml in the PTH-treated wild-type group. In contrast, serum aminoterminal propeptide of type 1 collagen and osteocalcin were equivalent in both groups. We conclude that, in the genetic absence of Rac2, the anabolic response to PTH is increased. This appears to be due to attenuated resorptive activity of osteoclasts.
Gonadotropin-Releasing Hormone Analog Structural Determinants of Selectivity for Inhibition of Cell Growth: Support for the Concept of Ligand-Induced Selective Signaling
Authors: López de Maturana Rakel , Pawson Adam J. , Lu Zhi-Liang , Davidson Lindsay , Maudsley Stuart , Morgan Kevin , Langdon Simon P. , Millar Robert P.
Published: May 2008

GnRH and its receptor are expressed in human reproductive tract cancers, and direct antiproliferative effects of GnRH analogs have been demonstrated in cancer cell lines. The intracellular signaling responsible for this effect differs from that mediating pituitary gonadotropin secretion. The GnRH structure-activity relationship is different for the two effects. Here we report a structure-activity relationship study of GnRH agonist antiproliferative action in model cell systems of rat and human GnRH receptors stably expressed in HEK293 cells. GnRH II was more potent than GnRH I in inhibiting cell growth in the cell lines. In contrast, GnRH I was more potent than GnRH II in stimulating inositol phosphate production, the signaling pathway in gonadotropes. The different residues in GnRH II (His5, Trp7, Tyr8) were introduced singly or in pairs into GnRH I. Tyr5 replacement by His5 produced the highest increase in the antiproliferative potency of GnRH I. Tyr8 substitution of Arg8 produced the most selective analog, with very poor inositol phosphate generation but high antiproliferative potency. In nude mice bearing tumors of the HEK293 cell line, GnRH II and an antagonist administration was ineffective in inhibiting tumor growth, but d-amino acid stabilized analogs (d-Lys6 and d-Arg6) ablated tumor growth. Docking of GnRH I and GnRH II to the human GnRH receptor molecular model revealed that Arg8 of GnRH I makes contact with Asp302, whereas Tyr8 of GnRH II appears to make different contacts, suggesting these residues stabilize different receptor conformations mediating differential intracellular signaling and effects on gonadotropin and cell growth. These findings provide the basis for the development of selective GnRH analog cancer therapeutics that directly target tumor cells or inhibit pituitary gonadotropins or do both.
Policy Influences on Community Trail Development
Authors: Eyler Amy A. , Brownson Ross C. , Evenson Kelly R. , Levinger David , Maddock Jay E. , Pluto Delores , Troped Philip J. , Schmid Thomas L. , Carnoske Cheryl , Richards Katherine L. , Steinman Lesley E.
Published: May 2008

This study explores processes and policies that facilitate the development of community trails. With funding from Active Living Research and the research framework of the Physical Activity Policy Research Network (PAPRN), we conducted a multiple-site case study. A total of six trails in Hawaii, Massachusetts, Missouri, North Carolina, South Carolina, and Washington were chosen for study. The goals of this case study were to identify the policy influences on trail development, explore the roles of key players in trail development, and compare and contrast findings from the different trails. Trail development can be a long process. Some of the trails took over a decade to complete because of funding, opposition, and roadblocks in the form of design standard policies. Work in trail development requires a team of many players, and it is necessary to balance their varied motives to accomplish a shared overall goal. Foresight through the master planning process is also a vital component of successful trail development. Finally, community involvement is key. Communities contemplating trail development should explore the effects of policy on the trail projects reported here to proactively identify potential influence.