bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic‐Pharmacodynamic Modeling of Morphine and Oxycodone Concentrations and Analgesic Effect in a Multimodal Experimental Pain Model
Authors: Staahl Camilla , Upton Richard , Foster David J. R. , Christrup Lona Louring , Kristensen Kim , Hansen Steen Honoré , Arendt‐Nielsen Lars , Drewes Asbjørn Mohr
Published: April 2008

Analgesia from most opioids is mediated by μ receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty‐four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2‐stage, nonlinear, mixed‐effects approach with an effect compartment to represent the concentration‐analgesia delay. Morphine kinetics was best described by a 2‐compartment model, whereas oxycodone kinetics was best described with a 1‐compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.
The Effect of Bis-(3-Triethoxysilylpropyl)— Tetrasulfide, Si69 on Properties of Recycled Poly (Vinyl chloride)/Acrylonitrile—Butadiene Rubber/Fly Ash (PVCr/NBR/FA) Composites
Authors: Ismail H. , Kheong O.W.
Published: April 2008

The effect of bis-(3-triethoxysilylpropyl)—tetrasulfide, Si69 on the tensile properties, swelling behavior and morphological characteristics of recycled poly(vinyl chloride)/acrylonitrile— butadiene rubber/fly ash (PVCr/NBR/FA) composites was studied. The composites were melt mixed at a temperature of 150°C and rotor speed of 50rpm. Si69 was used to improve the interaction between PVCr/NBR and FA. It was found that PVCr/NBR/FA + Si69 composites exhibit higher tensile strength, tensile modulus (M 100), and elongation at break, but lower swelling index than PVCr/NBR/FA composites without Si69. SEM study of the tensile fracture surfaces of the composites indicates that the presence of Si69 increased the interfacial interaction between PVCr/NBR and FA and also improved the dispersion of FA in PVCr/NBR matrix.
Effect of Thermal Fatigue on Tensile and Flexural Properties of Carbon/Cyanate Ester Pultruded Composite
Authors: Shivakumar Kunigal N. , Huanchun Chen  , Holloway Gary
Published: April 2008

The effect of thermal cycling on tensile and flexural properties of Cytec T650 carbon fiber/Lonza Primaset PT-30 cyanate ester pultruded composite rods proposed to be used for brush seals in gas turbine engines was evaluated. The thermal cycle consisted of 4min each of heating and cooling with 28min of hold at 315°C and 24min of hold at room temperature. Tension and three-point bend flexure tests were conducted after thermal cycling for 100, 200, 400, 600, and 800 cycles. Thermal cycling reduced the tensile strength and fracture strain almost linearly with the number of cycles while the tensile modulus remained unchanged. The flexural modulus did not change for the first 100 cycles and then decreased as much as 28% after 800 thermal cycles. Thermal cycling increased the Tg of the composite rods from 408 to 468°C. Optical and scanning electron microscopy analysis showed fiber/matrix interfacial separation and matrix shrinkage and oxidation due to thermal cycling.
A Re-examination of DMA Testing of Polymer Matrix Composites
Authors: Swaminathan Gowthaman , Shivakumar Kunigal
Published: April 2008

Dynamic Mechanical Analysis (DMA) is one of the most powerful tools to study the behavior of plastic and polymer composite materials. Unfortunately, as observed in literature and from author's experiences, there are discrepancies in the measurement of storage modulus using DMA, particularly for high modulus materials like carbon fiber composites. This is because of lack of guidelines for DMA testing of materials. This paper systematically studied the DMA testing of composites for both rectangular and cylindrical beam type specimens, identified the problems, made corrections and established simple test guidelines. Using these guidelines a wide variety of materials were tested and the test results are presented. Some of the test results were compared with the ASTM D790 bend test results.
Effect of Processing Conditions and Coupling Agents on ABS/SGF Composites Properties
Authors: Shokoohi Shirin , Arefazar Ahmad
Published: April 2008

Different samples of acrylonitrile-butadiene-styrene (ABS)/short glass fiber (SGF) composites were prepared. Varying processing conditions such as rotor rate, fiber volume, coupling agent type and amount, and also temperature were applied in order to investigate the effect of different factors on the final properties of the composite produced. All samples were tested physically, mechanically, and morphologically to investigate the effect of varying parameters mentioned above. The best fiber concentration, coupling agent, and temperature were found in a 30 wt% SGF composite coupled with 3 wt% of fiber tricholorovinyle silane and processed at 190°C (rotor rate = 80 rpm) which showed the best properties compared with other samples.
From Marginalized to Maximized Opportunities for Diverse Youths With Disabilities
Authors: Trainor Audrey A. , Lindstrom Lauren , Simon-Burroughs Marlene , Martin James E. , Sorrells Audrey McCray
Published: April 2008

Current secondary education and transition practices have created differential education and employment outcomes by gender, race and ethnicity, socioeconomic status, and disability classifications. These differential outcomes result in economic and social marginalization of far too many students with disabilities. Transition education practices need to respond to these differential outcomes and provide targeted, systematic, and long-term opportunities for all students to attain individually and family-determined postschool goals. This position paper recommends an ecological framework for considering the multiple systems that influence transition education and postschool outcomes for diverse youths with disabilities. The authors argue for educators, researchers, and policy makers to attend to social, political, economic, educational, and cultural contexts in developing effective interventions and improving postschool outcomes.
Improving Employment Outcomes of Individuals With Disabilities Through Short-Term Postsecondary Training
Authors: Flannery K. Brigid , Yovanoff Paul , Benz Michael R. , Kato Mary McGrath
Published: April 2008

Young adults with and without disabilities who complete postsecondary education, including occupational training, significantly improve their employment rates and financial well-being. This study examined employment outcomes and predictors of success for transition-aged and adult vocational rehabilitation consumers who participated in a college short-term training program. This program included key characteristics, making it a unique postsecondary option: an individualized design, a primarily worksite-based curriculum, and a focus on the existing labor market and employment. Results demonstrated successful participants had higher wages and worked more hours per quarter as well as more quarters during the first year after exit. Critical predictors for positive results were receipt of financial support, career services, and vocational coursework. The need for extensive work-related accommodations reduced the likelihood of success.
Teacher Candidates' Perceptions of Barriers to Effective Transition Programming
Authors: Wandry Donna L. , Webb Kristine W. , Williams Jane M. , Bassett Diane S. , Asselin Susan B. , Hutchinson Susan R.
Published: April 2008

Knowledge, skills, and competencies in transition planning are essential components of preparation programs for special and general educators. This study investigated teacher preparation, implementation of transition services, and perceived gaps in transition service delivery. Candidates in five special education preparation programs completed presemester and postsemester surveys to determine (a) the transition-related knowledge, skills, and competencies that candidates believe they are taught, (b) the transition competency level candidates believe they have, (c) facilitators and barriers to implementing transition practices, and (d) attitudes and perceptions about transition services and the candidates' related preparation. Results indicated that few candidates received any instruction in transition services prior to taking dedicated transition-related coursework. Candidates were not confident about their knowledge and skills in assessment, accountability, postschool outcomes, and student-focused planning and assessment.
On Mechanical Modeling of Cantilevered Piezoelectric Vibration Energy Harvesters
Authors: Erturk A. , Inman D.J.
Published: April 2008

Cantilevered beams with piezoceramic (PZT) layers are the most commonly investigated type of vibration energy harvesters. A frequently used modeling approach is the single-degree-of-freedom (SDOF) modeling of the harvester beam as it allows simple expressions for the electrical outputs. In the literature, since the base excitation on the harvester beam is assumed to be harmonic, the well known SDOF relation is employed for mathematical modeling. In this study, it is shown that the commonly accepted SDOF harmonic base excitation relation may yield highly inaccurate results for predicting the motion of cantilevered beams and bars. First, the response of a cantilevered Euler—Bernoulli beam to general base excitation given in terms of translation and small rotation is reviewed where more sophisticated damping models are considered. Then, the error in the SDOF model is shown and correction factors are derived for improving the SDOF harmonic base excitation model both for transverse and longitudinal vibrations. The formal way of treating the components of mechanical damping is also discussed. After deriving simple expressions for the electrical outputs of the PZT in open-circuit conditions, relevance of the electrical outputs to vibration mode shapes and the electrode locations is investigated and the issue of strain nodes is addressed.
Influence of Initial State on Position Regulation of Hysteretic Actuators
Authors: Gorbet R.B.
Published: April 2008

Actuators made from so-called smart materials have been proposed in the literature, for use in shape control of various surfaces. At the lowest level, this shape control problem can be thought of as a distributed regulation problem. Because of the hysteresis nonlinearity present in these actuators, there are an infinite number of input values corresponding to a particular output regulation setpoint. One might then ask the question, not relevant to memory-less systems, whether there is some advantage to regulating about one of these states in particular. This work proposes, based on observations from the Preisach model, that for any desired output there is one state in particular at which the system has a better natural (open-loop) rejection of uniformly-distributed noise at its input. This proposition is tested in both simulation and experiment. The reachability of this so-called `neutral state' is discussed, as is the generation of an input to drive the system to the appropriate neutral state. It is demonstrated that closed-loop regulation schemes will also benefit from starting in the appropriate neutral state, requiring less control effort for regulation.
Examining the Possible Corrosive Impact of Negative Advertising on Citizens' Attitudes toward Politics
Authors: Jackson Robert A. , Mondak Jeffery J. , Huckfeldt Robert
Published: April 2008

Negative campaign advertisements have been depicted by many observers as a scourge on American politics. One facet of the case against negative ads—that such commercials discourage voter turnout—has been studied extensively in the past decade. In contrast, a second criticism—that negative advertisements produce corrosive effects on mass attitudes—has received less attention. This is unfortunate as it would be highly consequential for American political behavior if exposure to negative campaign ads breeds widespread cynicism and antipathy toward politics, disapproval of political institutions and elected officials, and a decline in political efficacy. We examine these charges in the context of the 2002 U.S. midterm elections. Merging data on political ads from the 2002 rendition of the Wisconsin Advertising (WiscAds) Project with individual-level data collected via the 2002 Exercising Citizenship in American Democracy Survey, we devise a thorough and multifaceted test of the case against negative advertising. Our analyses do not provide empirical support for the charges levied against negative campaign ads.
The Viability Primary
Authors: Dowdle Andrew J. , Adkins Randall E. , Steger Wayne P.
Published: April 2008

Public support before the primaries is the strongest predictor of presidential candidate attrition and of the aggregate primary vote. Yet little is known about the factors that drive candidate preferences before the primaries. This article examines pre-primary candidate support in national Gallup polls for open presidential nomination races from 1976 to 2004. The study finds that candidate background characteristics have marginal effects on mass partisan support during the earliest phase of the nomination campaign and that campaign-related factors significantly affect pre-primary candidate support once the campaign begins. Prior levels of support, network news coverage, and party elite endorsements are significant factors in explaining variation in mass partisan support for candidates throughout the nomination campaign. The decisions of well-known, party “heavyweights” to enter or not enter the race affect the choices available to partisan voters and the overall competitiveness of the nomination campaign.
Effect of Nut Paste Enrichment on Wheat Dough Rheology and Bread Volume
Authors: Gómez M. , Oliete B. , Caballero P.A. , Ronda F. , Blanco C.A.
Published: April 2008

The study was carried out to investigate the effect of nuts (almond, hazelnut, peanut, walnut) enrichment (5, 10 and 15%) on the rheological properties of dough using alveograph, consistograph and rheofermentometer measurements. The loaf volume (LV) of bread added nut paste was also determined. The increase in nut percentage increases the dough viscoelastic characteristics (tenacity, extensibility, and strength) and mixing time, but decreased the dough consistency and tolerance, and the CO2 production during fermentation. Loaf volume increased when 5 and 10% of nut paste are added. Dough added walnut paste presented the lowest tenacity, strength and water absorption values, but the highest values in dough development time, tolerance and stability. Dough added almond, hazelnut and peanut paste had a similar behavior during mixing and handling.
Effects of Ingredient Incorporation into Sausage Meat on the Micellarisation and uptake of α-tocopherol by Caco-2 Human Intestinal Cells
Authors: Kenny O. , O'Callaghan Y. , O'Brien N.M.
Published: April 2008

Ingredients are incorporated into meat and meat products to produce a ``healthier'' product. However, the effect of ingredient addition on availability of nutrients endogenous to foods is generally not considered. This study investigated the availability and cellular uptake of α-tocopherol from supplemented sausages with the aid of an in vitro digestion procedure coupled with a Caco-2 cell model. Sausages were formulated with the addition of 3% or 10% ingredients (wheat bran, oat bran, soya protein, whey protein, olive oil, linseed oil, sunflower oil, and wheatgerm oil) and subjected to a two-phase in vitro system that simulates the digestive process in humans. Micelles were isolated from the digestate by ultracentrifugation. Of the ingredients selected for addition to sausage meat, only sunflower oil, and wheatgerm oil enhanced the micellarization of α-tocopherol, resulting in increased transfer from the test food to micelles. When ingredients were added at the 3% supplementation level, olive oil enhanced cellular uptake of α-tocopherol. Cellular uptake was not enhanced further with higher oil supplementation (3% vs. 10%). These results indicated that addition of ingredients to sausages (fibres, protein derivatives or vegetable oils) did not have a detrimental effect on α-tocopherol uptake and olive oil at the 3% supplementation level enhanced α-tocopherol availability.
A Mass-Transfer Model for the Drying of an Innovative Tomato Gel
Authors: Fiorentini C. , Díaz E. Leiva , Giner S.A.
Published: April 2008

Partially dehydrated tomato gels are innovative food products of extended shelf life for using in snack preparations. Flexible, sheet-shaped product was obtained by a pectic gelation mechanism induced by dehydration, starting from a formulation based on tomato puree. The drying kinetics of this product was studied in a bench-scale tray dryer operating between 40 and 80 °C at an air velocity of 2m/s. The `in-dryer' weighings of the trays allowed accurate experimental data to be recorded. The observed drying curves were modeled in two stages: for high moisture contents, with a constant drying rate model while at lower moistures, with an analytical-diffusive model, solved for the average sheet thickness. The mass-transfer Biot number in the diffusive model was found to be 1.1, indicating that external and internal resistances to mass-transfer are comparable. An Arrhenius model correctly described the temperature dependence of the water diffusion coefficient in the tomato pectic gel, represented by an activation energy of 22.0 kJ/mol. The model can be used to estimate minimum drying times and can be incorporated in tray dryer simulators for computer prototyping of new designs, and optimization of existing drying facilities.
Improvement in the Production of Smoked Trout Fillets (Salmo Gairdnerii) Steamed with Liquid Smoke
Authors: Dimitriadou D. , Zotos A. , Petridis D. , Taylor A.K.D.
Published: April 2008

A fish smoking process was applied using a combination of liquid smoke and steaming at pressures up to 1 bar above atmospheric pressure. Drying and brining prior to smoking have not shown any significant effect on the quality of the trout fillets. The nondried and dried for 4 h trout fillets prior to processing were assessed as slightly more acceptable products, processing yield, sensory analysis, instrumental color, pH, available lysine, polycyclic aromatic hydrocarbons (PAHs) and preservation time were estimated. The losses due to processing of the nondried samples were 23.7%, while 28.8% for those dried for 4h. The fillets processed at 1.5 and 2 bar steam pressure were assessed as highly acceptable. Lightness (L*) showed a decreasing trend due to pressure while redness (a*), and yellowness (b*) an increasing one. The destruction of available lysine was low (13.20% ± 1.01) and it was slightly dependent upon the process. No PAHs were detected. The preservation time, studied via total viable count, lactic acid bacteria, existence of Listeria monocytogenes, and sensory analysis, extended to more than 98 days at 4 ± 1 °C. The drying prior to processing seems to affect the preservation time. This processing technique is much simpler, faster, environmental effective, and leads to high quality smoked products.
Bridging the Cultural Gap in Management Consulting Research
Authors: Mohe Michael
Published: April 2008

Although there are underlying assumptions that culture plays an important role in management consulting, cultural aspects have not yet been addressed explicitly in management consulting research. This article aims to show that the phenomenon of management consulting is culturally determined to a significant extent. At the same time, it will become clear that consultancies have a strong influence on clients, as well as on countries and societies. This will be discussed with the help of a proposed framework, consisting of four levels of analysis. Finally, the article ends with implications for future research aiming to amplify the culture-based consulting research programme.
Likelihood to Sexually Harass
Authors: Luthar Harsh K. , Luthar Vipan K.
Published: April 2008

We tested hypotheses regarding the association of national culture with the likelihood to sexually harass by comparing samples of male and female international students. Our hypotheses were derived from implications of Hofstede's cross cultural dimension of power distance in light of the developing sexual harassment literature in an international context. One hundred and seventy eight American, Indian, and Chinese male and female students were administered the Likelihood to Sexually Harass (LSH) survey. Based on the results, most of our hypotheses were supported, although there was one unanticipated finding regarding female subjects. Our findings indicated that while males scored significantly higher than females on the LSH scale, nationality had a strong and independent effect on the LSH scores. Chinese and Indian males scored significantly higher on the LSH than American males. Chinese females scored significantly higher on the LSH instrument than American females. Hofstede's power distance dimension appears to capture an important aspect of national culture that shapes the perceptions and behaviors of both males and females in their proclivity to sexually exploit others with less power. Results and the limitations of the study as well as the future need to conduct sexual harassment research on diverse populations from different countries are discussed.
Interobserver and Intraobserver Variability in the Sonographic Measurement of the Size of the Thyroid Gland by Extended Field-of-View Sonography
Authors: Turgut Ahmet Tuncay , Coşkun Zafer Ünsal , Ergun Elif , Koşar Pinar , Geyik Pinar Özdemir , Görar Süheyla , Koşar Ugur
Published: April 2008

Significant intra- and interobserver variation has been reported for estimating the dimensions and the volume of the thyroid gland by conventional sonography in adults. This study aimed to assess the role of extended field-of-view (EFOV) sonography for evaluating the size of the thyroid gland. The mediolateral, anteroposterior, and craniocaudal diameters of both thyroid lobes as well as total thyroid volumes of 30 female patients with the clinical diagnosis of goiter were measured three times by three radiologists with the EFOV sonography technique. Based on these findings, the correlation between the measurements of different operators and different measurements of the same operator was investigated. The interobserver variations for craniocaudal diameters of the right and left thyroid lobes were 3.3% ± 1.9% (mean ± SD) and 2.8% ± 1.3% (mean ± SD), respectively ( P = .012), which were lower than the variations calculated for transverse and mediolateral diameters. The interobserver variation for the calculation of the total glandular volume was 6.3% ± 3.8% (mean ± SD). The intraobserver variations for the three radiologists assessing the total thyroid volume were 4.9% ± 3.0%, 4.2% ± 2.4%, and 4.5% ± 1.7% (all mean ± SD), respectively ( P = .521). EFOV sonography should be considered as an alternative technique for the dimension measurements of the thyroid gland, particularly in cases with goiter.
Fetal Bifid Left Ventricular Diverticulum Presenting With Ventricular Ectopy
Authors: Brucks Ulrike , Duval Jude , Roberson David , Cuneo Bettina F. , Husayni Tarek
Published: April 2008

We report the diagnosis and outcome of a fetus with an unusual left ventricular wall defect. A 34-week fetus presented for echocardiographic evaluation because of an irregular cardiac rhythm. Fetal echocardiography revealed frequent ventricular ectopy and an “accessory” ventricular chamber diagnosed as a left ventricular diverticulum (LVD). The ectopy resolved in utero but recurred after delivery. Angiography revealed a “bifid” LVD. Inderal therapy suppressed the ventricular ectopy. The association between ventricular ectopy and LVD is unusual, but the prognosis of LVD even with arrhythmia is excellent.
Measures of Association: How to Choose?
Authors: Khamis Harry
Published: April 2008

Researchers in sonography, as well as other areas, often wish to measure the strength of relationship or association between two variables. For example, one may wish to determine if, on the average, total cholesterol level increases as age increases for adult American men. However, there are a very large number of measures or coefficients (i.e., a number that indicates the strength of the relationship between two variables) from which to choose. It is not infrequent to find a researcher selecting an incorrect coefficient to measure a given association, thereby possibly rendering a false or misleading conclusion. The choice of the proper measure of association is based on, among other things, the characteristics of each of the two variables involved. This article enumerates every case that can be encountered by the researcher and provides an appropriate measure of association that can be used.
Multiple Osteochondromas: An Incidental Finding
Authors: Weinrich Brooke , Michael Kim
Published: April 2008

Multiple osteochondromas were detected during a lower extremity sonographic examination of a child with a palpable mass. An osteochondroma is a benign bone tumor that typically arises from the long bones, especially around the knee. Diagnosis is usually made during adolescence when a mass is palpated. Those affected are typically asymptomatic, but some experience pain, swelling, and possible pseudoaneurysm depending on the size and location of the lesion. Treatment is unnecessary unless symptomatic. Annual monitoring is necessary because a small percentage undergo malignant transformation. Sonography is not the modality of choice when imaging bone tumors, but it is important for sonographers to understand that bony abnormalities can be found in patients referred for evaluation of a palpable mass.
Pregnancy-Induced Accelerated Growth and Vascularity in a Thyroid Nodule
Authors: Kia Quek , Rathakrishnan Rahul , Hong Chiew , Sharma Vijay K.
Published: April 2008

Thyroid disorders are frequent in women, especially during the childbearing period. New nodules are known to develop in a significant proportion of pregnant women. Preexisting nodules may increase in size and vascularity during pregnancy. The authors describe a patient at 26 weeks' gestation living in a “relatively” iodine-sufficient area, with a large and highly vascular thyroid nodule but normal thyroid functions. Both vascularity and size revealed considerable reduction on a follow-up sonographic examination three months after the delivery.
Dominant negative Bmp5mutation reveals key role of BMPs in skeletal response to mechanical stimulation
Authors: Ho Andrew M , Marker Paul C , Peng Hairong , Quintero Andres J , Kingsley David M , Huard Johnny
Published: April 2008

Background

Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear.

Results

Here, we identify a novel germline mutation at the mouse Bone morphogenetic protein 5 (Bmp5) locus. Genetic analysis shows that the mutation occurs at a site encoding the proteolytic processing sequence of the BMP5 protein and blocks proper processing of BMP5. Anatomic studies reveal that this mutation affects the formation of multiple skeletal features including several muscle-induced skeletal sites in vivo. Biomechanical studies of osteoblasts from these anatomic sites show that the mutation inhibits the proper response of bone cells to mechanical stimulation.

Conclusion

The results from these genetic, biochemical, and biomechanical studies suggest that BMPs are required not only for skeletal patterning during embryonic development, but also for bone response and remodeling to mechanical stimulation at specific anatomic sites in the skeleton.
Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells
Authors: Masui Shinji , Ohtsuka Satoshi , Yagi Rika , Takahashi Kadue , Ko Minoru SH , Niwa Hitoshi
Published: April 2008

Background

Rex1/Zfp42 has been extensively used as a marker for the undifferentiated state of pluripotent stem cells. However, its function in pluripotent stem cells including embryonic stem (ES) cells remained unclear although its involvement in visceral endoderm differentiation in F9 embryonal carcinoma (EC) cells was reported.

Results

We showed the function of Rex1 in mouse ES cells as well as in embryos using the conventional gene targeting strategy. Our results clearly indicated that Rex1 function is dispensable for both the maintenance of pluripotency in ES cells and the development of embryos. However, Rex1-/- ES cells showed the defect to induce a subset of the marker genes of visceral endoderm, when differentiated as embryoid body, as found in EC cells.

Conclusion

Rex1 should be regarded just as a marker of pluripotency without functional significance like the activity of alkaline phosphatase.
Transcriptomic changes induced by acute ozone in resistant and sensitive Medicago truncatulaaccessions
Authors: Puckette Michael C , Tang Yuhong , Mahalingam Ramamurthy
Published: April 2008

Background

Tropospheric ozone, the most abundant air pollutant is detrimental to plant and animal health including humans. In sensitive plant species even a few hours of exposure to this potent oxidant (200–300 nL. L-1) leads to severe oxidative stress that manifests as visible cell death. In resistant plants usually no visible symptoms are observed on exposure to similar ozone concentrations. Naturally occurring variability to acute ozone in plants provides a valuable resource for examining molecular basis of the differences in responses to ozone. From our earlier study inMedicago truncatula, we have identified cultivar Jemalong is ozone sensitive and PI 464815 (JE154) is an ozone-resistant accession. Analyses of transcriptome changes in ozone-sensitive and resistant accession will provide important clues for understanding the molecular changes governing the plant responses to ozone.

Results

Acute ozone treatment (300 nL L-1for six hours) led to a reactive oxygen species (ROS) burst in sensitive Jemalong six hours post-fumigation. In resistant JE154 increase in ROS levels was much reduced compared to Jemalong. Based on the results of ROS profiling, time points for microarray analysis were one hour into the ozone treatment, end of treatment and onset of an ozone-induced ROS burst at 12 hours. Replicated temporal transcriptome analysis in these two accessions using 17 K oligonucleotide arrays revealed more than 2000 genes were differentially expressed. Significantly enriched gene ontologies (GOs) were identified using the Cluster Enrichment analysis program. A striking finding was the alacrity of JE154 in altering its gene expression patterns in response to ozone, in stark contrast to delayed transcriptional response of Jemalong. GOs involved in signaling, hormonal pathways, antioxidants and secondary metabolism were altered in both accessions. However, the repertoire of genes responding in each of these categories was different between the two accessions. Real-time PCR analysis confirmed the differential expression patterns of a subset of these genes.

Conclusion

This study provided a cogent view of the unique and shared transcriptional responses in an ozone-resistant and sensitive accession that exemplifies the complexity of oxidative signaling in plants. Based on this study, and supporting literature in Arabidopsis we speculate that plants sensitive to acute ozone are impaired in perception of the initial signals generated by the action of this oxidant. This in turn leads to a delayed transcriptional response in the ozone sensitive plants. In resistant plants rapid and sustained activation of several signaling pathways enables the deployment of multiple mechanisms for minimizing the toxicity effect of this reactive molecule.
Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q
Authors: Picelli Simone , Vandrovcova Jana , Jones Siân , Djureinovic Tatjana , Skoglund Johanna , Zhou Xiao-Lei , Velculescu Victor E , Vogelstein Bert , Lindblom Annika
Published: April 2008

Background

Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer.

Methods

Statistical analysis was performed using multipoint parametric and nonparametric linkage.

Results

Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1).

Conclusion

The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.
Quantifying hepatitis C transmission risk using a new weighted scoring system for the Blood-Borne Virus Transmission Risk Assessment Questionnaire (BBV-TRAQ): Applications for community-based HCV surveillance, education and prevention
Authors: Stoové Mark A , Fry Craig L , Lintzeris Nicholas
Published: April 2008

Background

The hepatitis C virus (HCV) is a major cause of drug-related morbidity and mortality, with incidence data implicating a wide range of HCV transmission risk practices. The Blood-Borne Virus Transmission Risk Assessment Questionnaire (BBV-TRAQ) is a content valid instrument that comprehensively assesses HCV risk practices. This study examines the properties of a new weighted BBV-TRAQ designed to quantify HCV transmission risk among injecting drug users (IDU).

Methods

Analyses of cross-sectional surveys of Australian IDU (N = 450) were used to generate normative data and explore the properties of a weighted BBV-TRAQ. Items weights were assigned according to expert key informant ratings of HCV risk practices performed during the development stages of the BBV-TRAQ. A range of item weights was tested and psychometric properties explored. A weighting scheme was recommended based on the plausibility of normative subscale data in relation to research evidence and the ability of BBV-TRAQ scores to discriminate between HCV positive and negative participants.

Results

While retaining the psychometric properties of the unweighted scale and demonstrating good internal reliability. By taking into account the relative transmission risk of a broad range of putative HCV practices, the weighted BBV-TRAQ produced promising predictive validity results among IDU based on self-report HCV status, particularly among young and less experienced injectors.

Conclusion

Brief, easy to administer and score, and inexpensive to apply, the utility of the BBV-TRAQ for community based education and prevention is enhanced by the application of item weights, potentially offering a valid surrogate measure for HCV infection among IDU.
Streamlining tasks and roles to expand treatment and care for HIV: randomised controlled trial protocol
Authors: Fairall Lara R , Bachmann Max O , Zwarenstein Merrick F , Lombard Carl J , Uebel Kerry , van Vuuren Cloete , Steyn Dewald , Boulle Andrew , Bateman Eric D
Published: April 2008

Background

A major barrier to accessing free government-provided antiretroviral treatment (ART) in South Africa is the shortage of suitably skilled health professionals. Current South African guidelines recommend that only doctors should prescribe ART, even though most primary care is provided by nurses. We have developed an effective method of educational outreach to primary care nurses in South Africa. Evidence is needed as to whether primary care nurses, with suitable training and managerial support, can initiate and continue to prescribe and monitor ART in the majority of ART-eligible adults.

Methods/design

This is a protocol for a pragmatic cluster randomised trial to evaluate the effectiveness of a complex intervention based on and supporting nurse-led antiretroviral treatment (ART) for South African patients with HIV/AIDS, compared to current practice in which doctors are responsible for initiating ART and continuing prescribing. We will randomly allocate 31 primary care clinics in the Free State province to nurse-led or doctor-led ART. Two groups of patients aged 16 years and over will be included: a) 7400 registering with the programme with CD4 counts of ≤ 350 cells/mL (mainly to evaluate treatment initiation) and b) 4900 already receiving ART (to evaluate ongoing treatment and monitoring). The primary outcomes will be time to death (in the first group) and viral suppression (in the second group). Patients' survival, viral load and health status indicators will be measured at least 6-monthly for at least one year and up to 2 years, using an existing province-wide clinical database linked to the national death register.

Trial registration

Controlled Clinical Trials ISRCTN46836853
An assessment of the quality of randomised controlled trials conducted in China
Authors: Zhang Dalu , Yin Peng , Freemantle Nick , Jordan Rachel , Zhong Nanshan , Cheng KK
Published: April 2008

Background

Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.

Methods

A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.

Results

Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.

Conclusion

Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained.
The many faces of ubiquitinated histone H2A: insights from the DUBs
Authors: Vissers Joseph HA , Nicassio Francesco , van Lohuizen Maarten , Di Fiore Pier Paolo , Citterio Elisabetta
Published: April 2008

Monoubiquitination of H2A is a major histone modification in mammalian cells. Understanding how monoubiquitinated H2A (uH2A) regulates DNA-based processes in the context of chromatin is a challenging question. Work in the past years linked uH2A to transcriptional repression by the Polycomb group proteins of developmental regulators. Recently, a number of mammalian deubiquitinating enzymes (DUBs) that catalyze the removal of ubiquitin from H2A have been discovered. These studies provide convincing evidence that H2A deubiquitination is connected with gene activation. In addition, uH2A regulatory enzymes have crucial roles in the cellular response to DNA damage and in cell cycle progression. In this review we will discuss new insights into uH2A biology, with emphasis on the H2A DUBs.
Prolonged, granulocyte–macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha
Authors: Parsonage Greg , Filer Andrew , Bik Magdalena , Hardie Debbie , Lax Sian , Howlett Katherine , Church Leigh D , Raza Karim , Wong See-Heng , Trebilcock Emily , Scheel-Toellner Dagmar , Salmon Mike , Lord Janet M , Buckley Christopher D
Published: April 2008

Introduction

A surprising feature of the inflammatory infiltrate in rheumatoid arthritis is the accumulation of neutrophils within synovial fluid and at the pannus cartilage boundary. Recent findings suggest that a distinct subset of IL-17-secreting T-helper cells (TH17 cells) plays a key role in connecting the adaptive and innate arms of the immune response and in regulating neutrophil homeostasis. We therefore tested the hypothesis that synovial fibroblasts bridge the biological responses that connect TH17 cells to neutrophils by producing neutrophil survival factors following their activation with IL-17.

Methods

IL-17-expressing cells in the rheumatoid synovium, and IL-17-expressing cells in the peripheral blood, and synovial fluid were examined by confocal microscopy and flow cytometry, respectively. Peripheral blood neutrophils were cocultured either with rheumatoid arthritis synovial fibroblasts (RASF) or with conditioned medium from RASF that had been pre-exposed to recombinant human IL-17, TNFα or a combination of the two cytokines. Neutrophils were harvested and stained with the vital mitochondrial dye 3,3'-dihexyloxacarbocyanine iodide before being enumerated by flow cytometry.

Results

TH17-expressing CD4+ cells were found to accumulate within rheumatoid synovial tissue and in rheumatoid arthritis synovial fluid. RASF treated with IL-17 and TNFα (RASFIL-17/TNF) effectively doubled the functional lifespan of neutrophils in coculture. This was entirely due to soluble factors secreted from the fibroblasts. Specific depletion of granulocyte–macrophage colony-stimulating factor from RASFIL-17/TNF-conditioned medium demonstrated that this cytokine accounted for approximately one-half of the neutrophil survival activity. Inhibition of phosphatidylinositol-3-kinase and NF-κB pathways showed a requirement for both signalling pathways in RASFIL-17/TNF-mediated neutrophil rescue.

Conclusion

The increased number of neutrophils with an extended lifespan found in the rheumatoid synovial microenvironment is partly accounted for by IL-17 and TNFα activation of synovial fibroblasts. TH17-expressing T cells within the rheumatoid synovium are likely to contribute significantly to this effect.
TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells
Authors: Howlin Jillian , Rosenkvist Jeanette , Andersson Tommy
Published: April 2008

Introduction

Amplification of the TNK2 gene in primary tumours correlates with poor prognosis. In accordance, TNK2 overexpression was shown to promote invasion of cancer cells – but the mechanism by which TNK2 mediates these effects is unresolved. TNK2 was suggested to regulate Cdc42-driven migration by activation of breast cancer antioestrogen resistance 1 (BCAR1); however, distinct from this effect is evidence for a role of TNK2 in the regulation of epidermal growth factor receptor (EGFR) endocytosis and degradation. In the present study we sought to investigate whether negative targeting of TNK2 by siRNA could be used to inhibit cancer cell invasion, to establish the contribution of its effect on the EGFR and to consequently attempt to resolve the issue of TNK2's mechanism of action.

Methods

We used siRNA to knockdown expression of TNK2 and its proposed effector BCAR1 in order to analyse the effect of this knockdown on cancer cell behaviour in vitro. We examined morphological changes using phase-contrast microscopy and immunohistochemistry. Functional parameters examined included apoptosis, proliferation, migration and invasion. We also performed flow cytometry analysis to examine EGFR cell surface expression and carried out western blot to examine the total EGFR levels.

Results

We observed that targeting of TNK2 by siRNA in breast cancer cells resulted in distinct morphological changes characterised by a stellate appearance and an absence of protrusions at membrane edges. These changes were not recapitulated upon siRNA targeting of BCAR1. We thus hypothesised that a component of the effects induced by TNK2 may be independent of BCAR1. Consistent with the idea of an alternative mechanism for TNK2, we observed that TNK2 associates with activated EGFR in breast cancer cells in a TNK2-kinase-independent manner. Furthermore, we demonstrated that TNK2 functions to maintain EGFRs on the cell surface. We could demonstrate that the main functional effect of activating these surface EGFRs in breast cancer cells is stimulation of migration. In accordance, TNK2 silencing by siRNA led to a significant reduction in cell surface EGFR and to a concomitant decrease in the migratory and invasive capacity of breast cancer cells.

Conclusion

Our data suggest that TNK2 can enhance migration and invasion of breast cancer cells via preservation of EGFR expression, notwithstanding its previously reported signalling via BCAR1, explaining its oncogenic behaviour in vitro and correlation with metastatic human breast cancer in vivo.