bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of silane coupling on the fundamental properties of wood flour reinforced polypropylene composites
Authors: Kim Tae-Woo , Lee Sun-Young , Chun Sang-Jin , Doh Geum-Hyun , Paik Ki-Hyon
Published: November 2010

Wood flour (WF) was chemically modified with silanes such as 3-aminopropyltriethoxysilane, 3-methacryloxypropyltrimethoxysilane, and vinyltrimethoxysilane. Polypropylene (PP) composites reinforced with the chemically modified WF were prepared by melt compounding and injection molding. The effects of the silane treatments on the fundamental properties of wood fiber-reinforced PP composites were investigated by the measurement of mechanical properties, water absorption (WA), thermal properties, and scanning electron microscope (SEM) analysis. Silane treatments significantly improved tensile, flexural, and impact strengths of the composites, but it was found that there is no distinct difference among silanes. Silane treatments provided the decreased WA of the composites. From thermogravimetric analysis, the effect of the silane treatments on the thermal properties of the composites was not observed. From differential scanning calorimetric analysis, crystallization temperature and crystallization enthalpy were increased by the silane treatments, and crystallinity was decreased by the treatments. SEM photomicrographs show the evidence of the improved mechanical and WA properties of the PP/WF composites by the silane coupling treatments.
Deriving a Third Force Approach to Child Development From the Works of Alfred Adler
Authors: DeRobertis Eugene M.
Published: November 2010

Alfred Adler has had an enormous influence on the humanistic movement in psychology, though this influence has not always been properly acknowledged. Adler is considered by some (e.g., Abraham Maslow) to be one of the founding fathers of the third force movement, as his Individual Psychology embodies many of the basic tenets of humanistic psychology. In this article, it is argued that Adler’s work not only embodies the fundamental principles of humanistic psychology but also houses a latent framework for interpreting child development. Accordingly, a third force perspective on child development is explicated from Adler’s works. It is further argued that Adler’s approach to child development was ahead of its time and is relevant today.
Virtual Government–Citizen Relations
Authors: Brainard Lori A. , McNutt John G.
Published: November 2010

Public administration theory and practice suggest that e-government, citizen participation, and government–citizen collaboration are contributing to a movement toward New Public Service—as opposed to Old Public Administration and New Public Management. We explore this by focusing on the relationship between the Washington, D.C., police and local residents via online discussion groups. We ask, How do police interact with citizens virtually? How are these interactions structured? and Are they informational, transactional, or collaborative? Using descriptive data and thread analysis, and drawing distinctions between districts, we conclude that the bulk of activity is informational, a fair amount of activity is transactional, and less activity is collaborative. Thus, the relationship most closely approximates Old Public Administration, rather than New Public Management or New Public Service. The evidence offers some cause for hope for the future of police–community relations in virtual space and ideas for future research.
The Bureau of Municipal Research and the Development of a Professional Public Service
Authors: McDonald Bruce D.
Published: November 2010

This article explores the professionalization of public administration in terms of its relation to the New York Bureau of Municipal Research. The formation of the New York Bureau of Municipal Research in 1907 served as the catalyst for the creation and expansion of a professional public service. Although public administration has failed to transform into a profession, this article shows that the Bureau contributed to professionalization by (a) developing a body of knowledge and theory for the field, (b) developing a school in which to train persons in that knowledge, and (c) promoting a place where the training and knowledge can be applied.
A non-linear observer for attitude estimation of a fixed-wing unmanned aerial vehicle without GPS measurements
Authors: Mahony R. , Euston M. , Kim Jonghyuk , Coote P. , Hamel T.
Published: November 2010

In this paper we propose a simple non-linear observer for attitude estimation based only on output from a typical inertial measurement unit (IMU) and dynamic pressure sensor embarked on a low-cost unmanned aerial vehicle. In particular, we aim to provide a good quality attitude estimate in the absence of global positioning system (GPS) ground truth and with potential low-frequency bias and high-frequency noise in the IMU sensor measurements. In addition, the case where the IMU only provides gyrometer and accelerometer outputs is considered; that is, there is no magnetometer output or it cannot be used due to local magnetic disturbances such as are common on a vehicle with electric motors. The proposed observer uses a simple centripetal force model (based on gyrometer and dynamic pressure measurements), augmented by a first-order dynamic model for angle of attack, to estimate non-inertial components of the acceleration. This estimate is used to correct the accelerometer output to provide a low-frequency estimate of the gravitational direction. This inertial direction, along with the gyrometer output, is then used to drive a fully non-linear attitude observer posed on the orthogonal group of rotation matrices SO(3). The observer is augmented with an integral state that ensures compensation of gyrometer bias. The resulting observer is simple to implement and fully non-linear. Experimental results are provided on a real-world data set and the performance of the filter is evaluated against the output from a full GPS/inertial navigation system (INS) that was available for the data set.
A fast and robust method for line detection based on image pyramid and Hough transform
Authors: Yan Zhiguo , Xu De , Tan Min
Published: November 2010

It is of great importance to locate lines quickly and robustly in images. In this paper, a new method based on a binary image pyramid and Hough transform is developed to extract lines fast and accurately in two steps. Lines are quickly detected via a two-dimensional Hough transform in a lower-resolution image on a pyramid's top, and then they are finely located via a one-dimensional Hough transform in the original image at the pyramid's bottom. The proposed method has good ability to detect lines in noisy images, with reduced computation cost and storage requirement. The performance analysis and experiments are provided to verify the effectiveness of the proposed method.
Arthroscopic Treatment of Osteochondral Lesions of the Ankle With Matrix-Associated Chondrocyte Implantation
Authors: Aurich Matthias , Bedi Harvinder S. , Smith Peter J. , Rolauffs Bernd , Mückley Thomas , Clayton James , Blackney Mark
Published: November 2010

Background: Conventional autologous chondrocyte transplantation in the ankle often requires tibial or fibular osteotomies with potential morbidity for the patient. Advances in biotechnology and surgical techniques have resulted in the development of matrix-associated chondrocyte implantation (MACI). As the chondrocyte-loaded scaffold can be applied arthroscopically, this procedure is especially useful for the treatment of osteochondral defects in the ankle.

Hypothesis: Arthroscopic MACI is a safe procedure in the ankle with good clinical and magnetic resonance imaging results.

Study Design: Case series; Level of evidence, 4.

Methods: The authors reviewed all patients (n = 18) who had arthroscopic MACI for osteochondral lesions of the ankle (n = 19) between February 2006 and May 2008 clinically and with magnetic resonance imaging. The pain and disability module of the Foot Function Index (FFI), the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating system, the Core Scale of the Foot and Ankle Module of the American Academy of Orthopaedic Surgeons (AAOS) Lower Limb Outcomes Assessment Instruments, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score were used. The clinical results up to 3 years after MACI (mean follow-up, 24.5 months) were compared with preoperative data for 14 cases and the magnetic resonance imaging data for all 19.

Results: A significant improvement (50.3% ± 13.2%) in all clinical scores was noted (FFI pain before MACI: 5.5 ± 2.0, after MACI: 2.8 ± 2.2; FFI disability before MACI: 5.0 ± 2.3, after MACI: 2.6 ± 2.2; AOFAS before MACI: 58.6 ± 16.1, after MACI: 80.4 ± 14.1; AAOS standardized mean before MACI: 59.9 ± 16.0, after MACI: 83.5 ± 13.2; AAOS normative score before MACI: 23.0 ± 13.0, after MACI: 42.2 ± 10.7). According to the AOFAS Hindfoot score, 64% were rated as excellent and good, whereas 36% were rated fair and poor. The results correlated with the age of the patient and the duration of symptoms, but not with the size of the lesion. Sixteen patients (89%) reported regular sports activities before the onset of symptoms; 13 of them (81%) returned to sports after the MACI, 56% (n = 9) to the same level. The mean MOCART score was 62.4 ± 15.8 points. In general, there was no relation between MOCART score and clinical outcome, although the filling of the defect showed some correlation with the AAOS score.

Conclusion: Arthroscopic MACI is a safe procedure for the treatment of osteochondral lesions in the ankle with overall good clinical and magnetic resonance imaging results.
Environmental compatibility of closed landfills - assessing future pollution hazards
Authors: Laner David , Fellner Johann , Brunner Paul H
Published: November 2010

Municipal solid waste landfills need to be managed after closure. This so-called aftercare comprises the treatment and monitoring of residual emissions as well as the maintenance and control of landfill elements. The measures can be terminated when a landfill does not pose a threat to the environment any more. Consequently, the evaluation of landfill environmental compatibility includes an estimation of future pollution hazards as well as an assessment of the vulnerability of the affected environment. An approach to assess future emission rates is presented and discussed in view of long-term environmental compatibility. The suggested method consists (a) of a continuous model to predict emissions under the assumption of constant landfill conditions, and (b) different scenarios to evaluate the effects of changing conditions within and around the landfill. The model takes into account the actual status of the landfill, hence different methods to gain information about landfill characteristics have to be applied. Finally, assumptions, uncertainties, and limitations of the methodology are discussed, and the need for future research is outlined.
Hospice Utilization and End-of-Life Care Decision Making of African Americans
Authors: Mazanec Polly M. , Daly Barbara J. , Townsend Aloen
Published: November 2010

Multiple, complex factors influence end-of-life (EOL) decisions for all persons. In the African American population, these factors include history of disparities and discrimination in health care, which may affect the individual and the family, family system beliefs, values, and practices, and health care system issues. Family dynamics have an especially important role in treatment decisions for loved ones with advanced disease. A family systems framework can guide the clinicians in appreciating care needs and preferences at EOL. Understanding why so many African Americans choose aggressive and often burdensome care, even at the expense of suffering, is important for communication about options at the EOL and the delivery of quality care at the EOL.
Substitutes for School Nurses in Illinois
Authors: Vollinger Linda Jeno , Bergren Martha Dewey , Belmonte-Mann Frances
Published: November 2010

The purpose of this descriptive study was to explore utilization of nurse substitutes in the school setting in Illinois. The literature described personnel who staff the school health office in the absence of the school nurse and the barriers to obtaining nurse substitutes. There were no empirical studies conducted on school nurse substitutes in the literature. Thus, a sample of 148 Illinois school nurses was recruited to complete a 20-item online survey. In the absence of a school nurse, 10.1% of health offices were not staffed, 37.8% were covered by a nurse who was simultaneously responsible for their usual assignment, and 25.7% were staffed by nonlicensed personnel. Therefore, 73.6% of the respondents' assignments had no registered nurse immediately available the most recent day the nurse was absent.
Effect of Assessment Task and Letter Writing Ability on Preschool Children’s Spelling Performance
Authors: Puranik Cynthia , Apel Kenn
Published: November 2010

The purpose of this study was to examine whether spelling performance in preschool children varied as a function of the method of assessment and letter writing ability. The authors manipulated the motoric element and memory demands of the task by having children spell single words using letter tiles, orally, and by writing. The authors also assessed their letter writing abilities. The results of this study indicated that spelling performance did not vary by task once children could write approximately 19 letters adequately. That is, once children reached a certain threshold of orthographic knowledge, the type of assessment task did not impact spelling outcomes. Prior to reaching that threshold, tile spelling was superior to oral and written spelling and oral spelling was superior to written spelling. This study provides additional evidence for the contention that letter writing ability is an orthographic knowledge skill rather than a pure motoric ability and that this linguistic skill influences spelling outcomes.
Second Graders as Spellers: What Types of Errors Are They Making?
Authors: Arndt Elissa J. , Foorman Barbara R.
Published: November 2010

Beginning second-grade students ( N = 60) were administered a researcher-developed, dictated spelling test. Spelling errors of students were analyzed by grade-level spelling patterns and linguistic characteristics: phonological, orthographic, orthographic image, transposition, and morphological. Results revealed that morphological spelling pattern errors occurred most frequently. The frequency of linguistic category errors for this sample, ranging from least to most, was transposition, phonological, orthographic image, orthographic, and morphological. Further analysis of the bottom quarter of students, as determined by their performance on a timed word reading measure, indicated a pattern of spelling errors similar to the rest of the sample, but occurring in significantly greater quantity on average. These findings support previous research suggesting poor spellers display similar error patterns as better spelling peers, but with higher frequency. Initial implications suggest to educators that in spite of the wide range of spelling ability in their classrooms, the pattern of knowledge appears similar. Students rely on multiple sources of linguistic knowledge, and by analyzing their spelling errors based on the information students use to generate their spellings, instruction may be provided to explicitly and systematically target students’ weaknesses.
With or Without You
Authors: Wyer Natalie A. , Perfect Timothy J. , Neilens Helen , Mazzoni Giuliana , Roper Jean
Published: November 2010

The present research was designed to investigate the consequences of suppressing social stereotypes on behavior in intrapersonal and interpersonal contexts. In two experiments, the authors manipulated the behavioral context in which postsuppression effects were measured. In intrapersonal contexts, postsuppression behavior was consistent with the suppressed stereotype ( assimilation behavior). Conversely, in interpersonal contexts, postsuppression behavior was appropriate to interacting with a member of the group whose stereotype was suppressed ( response behavior). The authors conclude that stereotypes activated via suppression can alter one’s behavior in multiple ways, depending on the context in which the behavior takes place.
Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort
Authors: Bernaudin Françoise , Verlhac Suzanne , Arnaud Cécile , Kamdem Annie , Chevret Sylvie , Hau Isabelle , Coïc Lena , Leveillé Emmanuella , Lemarchand Elisabeth , Lesprit Emmanuelle , Abadie Isabelle , Medejel Nadia , Madhi Fouad , Lemerle Sophie , Biscardi Sandra , Bardakdjian Josiane , Galactéros Frédéric , Torres Martine , Kuentz Mathieu , Ferry Christelle , Socié Gérard , Reinert Philippe , Delacourt Christophe
Published: November 2010

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sβ0), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 109/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.
The hemostatic status of pediatric recipients of adult liver grafts suggests that plasma levels of hemostatic proteins are not regulated by the liver
Authors: Lisman Ton , Platto Marco , Meijers Joost C. M. , Haagsma Elizabeth B. , Colledan Michele , Porte Robert J.
Published: November 2010

Plasma levels of coagulation factors differ profoundly between adults and children, but are remarkably stable throughout adulthood. It is unknown which factors determine plasma levels of coagulation factors in a given individual. We hypothesized that the liver, which synthesizes coagulation factors, also controls plasma levels. We measured a panel of coagulation factors in samples taken from either adults or young children who underwent a liver transplantation with adult donor livers. Samples were taken 1-3 months after transplantation, when the patients were clinically stable with adequate graft function. After liver transplantation, the hemostatic profile of the pediatric group was remarkably different from that of the adult group, and resembled the hemostatic profile of normal children. Thus, children transplanted with an adult liver graft maintain a pediatric hemostatic profile after transplantation despite receiving an adult liver graft. These findings suggest that plasma levels of hemostatic proteins are not controlled by the liver.
Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia
Authors: Makani Julie , Menzel Stephan , Nkya Siana , Cox Sharon E. , Drasar Emma , Soka Deogratius , Komba Albert N. , Mgaya Josephine , Rooks Helen , Vasavda Nisha , Fegan Gregory , Newton Charles R. , Farrall Martin , Lay Thein Swee
Published: November 2010

Fetal hemoglobin (HbF, α2γ2) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.
Introgressive hybridization and the evolutionary history of the herring gull complex revealed by mitochondrial and nuclear DNA
Authors: Sternkopf Viviane , Liebers-Helbig Dorit , Ritz Markus S , Zhang Jun , Helbig Andreas J , de Knijff Peter
Published: November 2010

Background

Based on extensive mitochondrial DNA (mtDNA) sequence data, we previously showed that the model of speciation among species of herring gull (Larus argentatus) complex was not that of a ring species, but most likely due more complex speciation scenario's. We also found that two species, herring gull and glaucous gull (L. hyperboreus) displayed an unexpected biphyletic distribution of their mtDNA haplotypes. It was evident that mtDNA sequence data alone were far from sufficient to obtain a more accurate and detailed insight into the demographic processes that underlie speciation of this complex, and that extensive autosomal genetic analysis was warranted.

Results

For this reason, the present study focuses on the reconstruction of the phylogeographic history of a limited number of gull species by means of a combined approach of mtDNA sequence data and 230 autosomal amplified fragment length polymorphism (AFLP) loci. At the species level, the mtDNA and AFLP genetic data were largely congruent. Not only for argentatus and hyperboreus, but also among a third species, great black-backed gull (L. marinus) we observed two distinct groups of mtDNA sequence haplotypes. Based on the AFLP data we were also able to detect distinct genetic subgroups among the various argentatus, hyperboreus, and marinus populations, supporting our initial hypothesis that complex demographic scenario's underlie speciation in the herring gull complex.

Conclusions

We present evidence that for each of these three biphyletic gull species, extensive mtDNA introgression could have taken place among the various geographically distinct subpopulations, or even among current species. Moreover, based on a large number of autosomal AFLP loci, we found evidence for distinct and complex demographic scenario's for each of the three species we studied. A more refined insight into the exact phylogeographic history within the herring gull complex is still impossible, and requires detailed autosomal sequence information, a topic of our future studies.
Contemporary temperature-driven divergence in a Nordic freshwater fish under conditions commonly thought to hinder adaptation
Authors: Kavanagh Kathryn D , Haugen Thrond O , Gregersen Finn , Jernvall Jukka , Vøllestad L Asbjørn
Published: November 2010

Background

Evaluating the limits of adaptation to temperature is important given the IPCC-predicted rise in global temperatures. The rate and scope of evolutionary adaptation can be limited by low genetic diversity, gene flow, and costs associated with adaptive change. Freshwater organisms are physically confined to lakes and rivers, and must therefore deal directly with climate variation and change. In this study, we take advantage of a system characterised by low genetic variation, small population size, gene flow and between-trait trade-offs to study how such conditions affect the ability of a freshwater fish to adapt to climate change. We test for genetically-based differences in developmental traits indicating local adaptation, by conducting a common-garden experiment using embryos and larvae from replicate pairs of sympatric grayling demes that spawn and develop in natural cold and warm water, respectively. These demes have common ancestors from a colonization event 22 generations ago. Consequently, we explore if diversification may occur under severely constraining conditions.

Results

We found evidence for divergence in ontogenetic rates. The divergence pattern followed adaptation predictions as cold-deme individuals displayed higher growth rates and yolk conversion efficiency than warm-deme individuals at the same temperature. The cold-deme embryos had a higher rate of muscle mass development. Most of the growth- and development differences occurred prior to hatch. The divergence was probably not caused by genetic drift as there was a strong degree of parallelism in the divergence pattern and because phenotypic differentiation (QST) was larger than estimated genetic drift levels (microsatellite FST) between demes from different temperature groups. We also document that these particular grayling populations cannot develop successfully at temperatures above 12°C, whereas other European populations can, and that increasing the muscle mass development rate comes at the cost of some skeletal trait development rates.

Conclusions

This study shows that genetically based phenotypic divergence can prevail even under conditions of low genetic variation and ongoing gene flow. Furthermore, population-specific maximum development temperatures along with musculoskeletal developmental trade-offs may constrain adaptation.
Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence
Authors: Boyle James P , Thompson Theodore J , Gregg Edward W , Barker Lawrence E , Williamson David F
Published: November 2010

Background

People with diabetes can suffer from diverse complications that seriously erode quality of life. Diabetes, costing the United States more than $174 billion per year in 2007, is expected to take an increasingly large financial toll in subsequent years. Accurate projections of diabetes burden are essential to policymakers planning for future health care needs and costs.

Methods

Using data on prediabetes and diabetes prevalence in the United States, forecasted incidence, and current US Census projections of mortality and migration, the authors constructed a series of dynamic models employing systems of difference equations to project the future burden of diabetes among US adults. A three-state model partitions the US population into no diabetes, undiagnosed diabetes, and diagnosed diabetes. A four-state model divides the state of "no diabetes" into high-risk (prediabetes) and low-risk (normal glucose) states. A five-state model incorporates an intervention designed to prevent or delay diabetes in adults at high risk.

Results

The authors project that annual diagnosed diabetes incidence (new cases) will increase from about 8 cases per 1,000 in 2008 to about 15 in 2050. Assuming low incidence and relatively high diabetes mortality, total diabetes prevalence (diagnosed and undiagnosed cases) is projected to increase from 14% in 2010 to 21% of the US adult population by 2050. However, if recent increases in diabetes incidence continue and diabetes mortality is relatively low, prevalence will increase to 33% by 2050. A middle-ground scenario projects a prevalence of 25% to 28% by 2050. Intervention can reduce, but not eliminate, increases in diabetes prevalence.

Conclusions

These projected increases are largely attributable to the aging of the US population, increasing numbers of members of higher-risk minority groups in the population, and people with diabetes living longer. Effective strategies will need to be undertaken to moderate the impact of these factors on national diabetes burden. Our analysis suggests that widespread implementation of reasonably effective preventive interventions focused on high-risk subgroups of the population can considerably reduce, but not eliminate, future increases in diabetes prevalence.
Age-dependent changes in TDP-43 levels in a mouse model of Alzheimer disease are linked to Aβ oligomers accumulation
Authors: Caccamo Antonella , Magrí Andrea , Oddo Salvatore
Published: November 2010

Background

Transactive response DNA-binding protein 43 (TDP-43) is the pathological protein found in frontotemporal lobar degeneration with ubiquitin positive inclusions and in amyotrophic lateral sclerosis. In diseased tissue, TDP-43 translocates from its physiological nuclear location into the cytoplasm, where it accumulates. Additionally, C-terminal fragments of TDP-43 accumulate in affected brain regions and are sufficient to cause TDP-43 mislocalization and cytoplasmic accumulationin vitro. TDP-43 also accumulates in 30% of Alzheimer disease (AD) cases, a finding that has been highly reproducible. The role of TDP-43 in AD and its relation with Aβ and tau pathology, the two neuropathological hallmarks of AD, remains to be elucidated.

Results

Here we show that levels of TDP-43 and its ~35 kDa C-terminal fragment are significantly increased in the 3×Tg-AD mice, an animal model of AD that develops an age-dependent cognitive decline linked to the accumulation of Aβ and tau. We also report that the levels of TDP-43 and its C-terminal fragment correlate with the levels of soluble Aβ oligomers, which play a key role in AD pathogenesis. Notably, genetically reducing Aβ42production restores the levels of TDP-43 and its ~35 kDa C-terminal fragment to control levels.

Conclusions

These data suggest a possible relation between Aβ oligomers and TDP-43.
Urokinase-type plasminogen activator and arthritis progression: contrasting roles in systemic and monoarticular arthritis models
Authors: De Nardo Christine M , Lenzo Jason C , Pobjoy Jarrad , Hamilton John A , Cook Andrew D
Published: November 2010

Introduction

Urokinase-type plasminogen activator (u-PA) has been implicated in tissue destruction/remodeling. The absence of u-PA results in resistance of mice to systemic immune complex-driven arthritis models; monoarticular arthritis models involving an intra-articular (i.a.) antigen injection, on the other hand, develop more severe arthritis in its absence. The aims of the current study are to investigate further these contrasting roles that u-PA can play in the pathogenesis of inflammatory arthritis and to determine whether u-PA is required for the cartilage and bone destruction associated with disease progression.

Methods

To determine how the different pathogenic mechanisms leading to arthritis development in the different models may explain the contrasting requirement for u-PA, the systemic, polyarticular, immune complex-driven K/BxN arthritis model was modified to include an i.a. injection of saline as a local trauma in u-PA-/- mice. This modified model and the antigen-induced arthritis (AIA) model were also used in u-PA-/- mice to determine the requirement for u-PA in joint destruction. Disease severity was determined by clinical and histologic scoring. Fibrin(ogen) staining and the matrix metalloproteinase (MMP)-generated neoepitope DIPEN staining were performed by immunohistochemistry. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitative PCR.

Results

In our modified arthritis model, u-PA-/- mice went from being resistant to arthritis development following K/BxN serum transfer to being susceptible following the addition of an i.a. injection of saline. u-PA-/- mice also developed more sustained AIA compared with C57BL/6 mice, including reduced proteoglycan levels and increased bone erosions, fibrin(ogen) deposition and DIPEN expression. Synovial gene expression of the proinflammatory mediators (TNF and IL-1β), aggrecanases (ADAMTS-4 and -5) and MMPs (MMP3 and MMP13) were all sustained over time following AIA induction in u-PA-/- mice compared with C57BL/6 mice.

Conclusions

We propose that u-PA has a protective role in arthritis models with 'wound healing-like' processes following local trauma, possibly through u-PA/plasmin-mediated fibrinolysis, but a deleterious role in systemic models that are critically dependent on immune complex formation and complement activation. Given that cartilage proteoglycan loss and bone erosions were present and sustained in u-PA-/- mice with monoarticular arthritis, it is unlikely that u-PA/plasmin-mediated proteolysis is contributing directly to this tissue destruction/remodeling.
Resolution and uncertainty in 1D CSEM inversion: A Bayesian approach and open-source implementation
Authors: Gunning James , Glinsky Michael E. , Hedditch John
Published: November 2010

Resolution and uncertainty in controlled-source electromagnetic (CSEM) inversion is most naturally approached using a Bayesian framework. Resolution can be inferred by hierarchical models with free parameters for effective correlation lengths (“Bayesian smoothing”), or model-choice frameworks applied to variable resolution spatial models (Bayesian splitting/merging). Typical 1D CSEM data can be modeled with quite parsimonious models, typically O(10) parameters per common midpoint. Efficient optimizations for the CSEM problem must address the challenges of poor scaling, strong nonlinearity, multimodality and the necessity of bound constraints. The posterior parameter uncertainties are frequently controlled by the nonlinearity, and linearized approaches to uncertainty usually are very poor. In Markov Chain Monte Carlo (MCMC) approaches, the nonlinearity and poor scaling make good mixing hard to achieve. A novel, approximate frequentist method we call the Bayesianized parametric bootstrap (sometimes called randomized maximum likelihood) is much more efficient than MCMC in this problem, considerably better than linearized analysis but tends to modestly overstate uncertainties. The software that implements these ideas for the 1D CSEM problem is made available under an open-source license agreement.
Multiple prediction and subtraction from apparent slowness relations in 2D synthetic and field ocean-bottom cable data
Authors: Cao Juanjuan , McMechan George
Published: November 2010

A target-oriented algorithm is developed for the prediction of multiples recorded on ocean-bottom cables by utilizing apparent slowness relations in common-source and common-receiver gathers. It is based on combining offsets and times of direct waves and primary reflections to predict multiples by matching apparent slownesses at all source and receiver locations; all higher-order multiples can be predicted by matching apparent slownesses alternately in common-source and common-receiver gathers. No knowledge of the subsurface velocity is required. Traveltimes of the direct waves and primary reflections need to be picked from common-source gathers. The subtraction of multiples involves flattening the predicted times of the multiple events, subtracting a local spatial average trace from each trace, within a fixed time window containing the wavelet of the multiple, and then shifting the data back to its original times. Tests of synthetic and field data indicate that the proposed method predicts multiples very well and removes them from seismic data efficiently with negligible affect on the primary reflections, as long as the primary and multiple reflections do not overlap in time and slowness over substantial windows in the domain in which the removal is done.
17β-Estradiol Regulates Rat Growth Plate Chondrocyte Apoptosis Through a Mitochondrial Pathway Not Involving Nitric Oxide or MAPKs
Authors: Zhong M. , Carney D. H. , Boyan B. D. , Schwartz Z.
Published: November 2010

Estrogens cause growth plate closure in both males and females, by decreasing proliferation and inducing apoptosis of postproliferative growth plate chondrocytes. In vitro studies using 17β-estradiol (E2) conjugated to bovine serum albumin (E2-BSA) show that rat costochondral growth plate resting zone chondrocytes also respond to E2. Moreover, they are regulated by E2-BSA via a protein kinase C and ERK MAPK signaling pathway that is functional only in female cells. To better understand how E2 regulates apoptosis of growth plate chondrocytes, rat resting zone chondrocytes cells were treated with E2 or E2-BSA. E2 caused apoptosis in male and female resting zone and growth zone chondrocytes in a dose-dependent manner, based on elevated DNA fragmentation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-3 activation. E2 also up-regulated p53 and Bax protein (Bcl-2-associated X protein) levels and induced release of cytochrome C from the mitochondria, indicating a mitochondrial apoptotic pathway. The apoptotic effect of E2 did not involve elevated nitric oxide production or MAPKs. It was reduced by ICI 182780, which is an estrogen receptor (ER) antagonist and blocked by antibodies to Erα36, a membrane-associated ER. E2-BSA reduced cell viability and increased caspase-3 activity; ICI 182780 had no effect, but anti-ERα36 antibodies blocked the effect. The results indicate that estrogen is able to directly affect the cell population kinetics of growth plate chondrocytes by regulating apoptosis, as well as proliferation and differentiation in both resting zone and growth zone cells. They also have provided further information about the physiological functions of estrogen on longitudinal bone growth.
GPR119 Regulates Murine Glucose Homeostasis Through Incretin Receptor-Dependent and Independent Mechanisms
Authors: Flock Grace , Holland Dianne , Seino Yutaka , Drucker Daniel J.
Published: November 2010

G protein-coupled receptor 119 (GPR119) was originally identified as a β-cell receptor. However, GPR119 activation also promotes incretin secretion and enhances peptide YY action. We examined whether GPR119-dependent control of glucose homeostasis requires preservation of peptidergic pathways in vivo. Insulin secretion was assessed directly in islets, and glucoregulation was examined in wild-type (WT), single incretin receptor (IR) and dual IR knockout (DIRKO) mice. Experimental endpoints included plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY. Gastric emptying was assessed in WT, Glp1r−/−, DIRKO, Glp2r−/−, and GPR119−/− mice treated with the GPR119 agonist AR231453. AR231453 stimulated insulin secretion from WT and DIRKO islets in a glucose-dependent manner, improved glucose homeostasis, and augmented plasma levels of GLP-1, GIP, and insulin in WT and Gipr−/−mice. In contrast, although AR231453 increased levels of GLP-1, GIP, and insulin, it failed to lower glucose in Glp1r−/− and DIRKO mice. Furthermore, AR231453 did not improve ip glucose tolerance and had no effect on insulin action in WT and DIRKO mice. Acute GPR119 activation with AR231453 inhibited gastric emptying in Glp1r−/−, DIRKO, Glp2r−/−, and in WT mice independent of the Y2 receptor (Y2R); however, AR231453 did not control gastric emptying in GPR119−/− mice. Our findings demonstrate that GPR119 activation directly stimulates insulin secretion from islets in vitro, yet requires intact IR signaling and enteral glucose exposure for optimal control of glucose tolerance in vivo. In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis.
The Jumping SHOX Gene—Crossover in the Pseudoautosomal Region Resulting in Unusual Inheritance of Leri-Weill Dyschondrosteosis
Authors: Kant Sarina G. , van der Kamp Hetty J. , Kriek Marjolein , Bakker Egbert , Bakker Boudewijn , Hoffer Mariette J. V. , van Bunderen Patrick , Losekoot Monique , Maas Saskia M. , Wit Jan M. , Rappold Gudrun , Breuning Martijn H.
Published: November 2010

abstract

Context:

During meiosis I, the recombination frequency in the pseudoautosomal region on Xp and Yp (PAR1) in males is very high. As a result, mutated genes located within the PAR1 region can be transferred from the Y-chromosome to the X-chromosome and vice versa.

Patients:

Here we describe three families with SHOX abnormalities resulting in Leri-Weill dyschondrosteosis or Langer mesomelic dysplasia.

Results:

In about half of the segregations investigated, a transfer of the SHOX abnormality to the alternate sex chromosome was demonstrated.

Conclusions:

Patients with an abnormality of the SHOX gene should receive genetic counseling as to the likelihood that they may transmit the mutation or deletion to a son as well as to a daughter.
Pak1 control of E-cadherin endocytosis regulates salivary gland lumen size and shape
Authors: Pirraglia Carolyn , Walters Jenna , Myat Monn Monn
Published: November 2010

Generating and maintaining proper lumen size and shape in tubular organs is essential for organ function. Here, we demonstrate a novel role for p21-activated kinase 1 (Pak1) in defining the size and shape of the Drosophila embryonic salivary gland lumen by regulating the size and elongation of the apical domain of individual cells. Pak1 mediates these effects by decreasing and increasing E-cadherin levels at the adherens junctions and basolateral membrane, respectively, through Rab5- and Dynamin-dependent endocytosis. We also demonstrate that Cdc42 and Merlin act together with Pak1 to control lumen size. A role for Pak1 in E-cadherin endocytosis is supported by our studies of constitutively active Pak1, which induces the formation of multiple intercellular lumens in the salivary gland in a manner dependent on Rab5, Dynamin and Merlin. These studies demonstrate a novel and crucial role for Pak1 and E-cadherin endocytosis in determining lumen size and shape, and also identify a mechanism for multiple lumen formation, a poorly understood process that occurs in normal embryonic development and pathological conditions.
The Hippo pathway regulates intestinal stem cell proliferation duringDrosophilaadult midgut regeneration
Authors: Shaw Rachael L. , Kohlmaier Alexander , Polesello Cédric , Veelken Cornelia , Edgar Bruce A. , Tapon Nicolas
Published: November 2010

Intestinal stem cells (ISCs) in the adult Drosophila midgut proliferate to self-renew and to produce differentiating daughter cells that replace those lost as part of normal gut function. Intestinal stress induces the activation of Upd/Jak/Stat signalling, which promotes intestinal regeneration by inducing rapid stem cell proliferation. We have investigated the role of the Hippo (Hpo) pathway in the Drosophila intestine (midgut). Hpo pathway inactivation in either the ISCs or the differentiated enterocytes induces a phenotype similar to that observed under stress situations, including increased stem cell proliferation and expression of Jak/Stat pathway ligands. Hpo pathway targets are induced by stresses such as bacterial infection, suggesting that the Hpo pathway functions as a sensor of cellular stress in the differentiated cells of the midgut. In addition, Yki, the pro-growth transcription factor target of the Hpo pathway, is required in ISCs to drive the proliferative response to stress. Our results suggest that the Hpo pathway is a mediator of the regenerative response in the Drosophila midgut.
dFMRP and Caprin, translational regulators of synaptic plasticity, control the cell cycle at the Drosophila mid-blastula transition
Authors: Papoulas Ophelia , Monzo Kathryn F. , Cantin Greg T. , Ruse Cristian , Yates John R. , Ryu Young Hee , Sisson John C.
Published: November 2010

The molecular mechanisms driving the conserved metazoan developmental shift referred to as the mid-blastula transition (MBT) remain mysterious. Typically, cleavage divisions give way to longer asynchronous cell cycles with the acquisition of a gap phase. In Drosophila, rapid synchronous nuclear divisions must pause at the MBT to allow the formation of a cellular blastoderm through a special form of cytokinesis termed cellularization. Drosophila Fragile X mental retardation protein (dFMRP; FMR1), a transcript-specific translational regulator, is required for cellularization. The role of FMRP has been most extensively studied in the nervous system because the loss of FMRP activity in neurons causes the misexpression of specific mRNAs required for synaptic plasticity, resulting in mental retardation and autism in humans. Here, we show that in the early embryo dFMRP associates specifically with Caprin, another transcript-specific translational regulator implicated in synaptic plasticity, and with eIF4G, a key regulator of translational initiation. dFMRP and Caprin collaborate to control the cell cycle at the MBT by directly mediating the normal repression of maternal Cyclin B mRNA and the activation of zygotic frühstart mRNA. These findings identify two new targets of dFMRP regulation and implicate conserved translational regulatory mechanisms in processes as diverse as learning, memory and early embryonic development.
Ongoing roles of Phox2 homeodomain transcription factors during neuronal differentiation
Authors: Coppola Eva , d'Autréaux Fabien , Rijli Filippo M. , Brunet Jean-François
Published: November 2010

Transcriptional determinants of neuronal identity often stay expressed after their downstream genetic program is launched. Whether this maintenance of expression plays a role is for the most part unknown. Here, we address this question for the paralogous paired-like homeobox genes Phox2a and Phox2b, which specify several classes of visceral neurons at the progenitor stage in the central and peripheral nervous systems. By temporally controlled inactivation of Phox2b, we find that the gene, which is required in ventral neural progenitors of the hindbrain for the production of branchio-visceral motoneuronal precursors, is also required in these post-mitotic precursors to maintain their molecular signature – including downstream transcription factors – and allow their tangential migration and the histogenesis of the corresponding nuclei. Similarly, maintenance of noradrenergic differentiation during embryogenesis requires ongoing expression of Phox2b in sympathetic ganglia, and of Phox2a in the main noradrenergic center, the locus coeruleus. These data illustrate cases where the neuronal differentiation program does not unfold as a transcriptional `cascade' whereby downstream events are irreversibly triggered by an upstream regulator, but instead require continuous transcriptional input from it.