bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Trait Loci for Femoral and Lumbar Vertebral Bone Mineral Density in C57BL/6J and C3H/HeJ Inbred Strains of Mice
Authors: Beamer Wesley G. , Shultz Kathryn L. , Donahue Leah Rae , Churchill Gary A. , Sen Saunak , Wergedal Jon R. , Baylink David J. , Rosen Clifford J.
Published: April 2006

Significant differences in vertebral (9%) and femoral (50%) adult bone mineral density (BMD) between the C57BL/6J (B6) and C3H/HeJ (C3H) inbred strains of mice have been subjected to genetic analyses for quantitative trait loci (QTL). Nine hundred eighty-six B6C3F2 females were analyzed to gain insight into the number of genes that regulate peak BMD and their locations. Femurs and lumbar vertebrae were isolated from 4-month-old B6C3F2 females at skeletal maturity and then BMD was determined by peripheral quantitative computed tomography (pQCT). Estimates of BMD heritability were 83% for femurs and 72% for vertebrae. Genomic DNA from F2 progeny was screened for 107 polymerase chain reaction (PCR)–based markers discriminating B6 and C3H alleles on all 19 autosomes. The regression analyses of markers on BMD revealed ten chromosomes (1, 2, 4, 6, 11, 12, 13, 14, 16, and 18) carrying QTLs for femurs and seven chromosomes (1, 4, 7, 9, 11, 14, and 18) carrying QTLs for vertebrae, each with log10 of the odds ratio (LOD) scores of 2.8 or better. The QTLs on chromosomes (Chrs) 2, 6, 12, 13, and 16 were unique to femurs, whereas the QTLs on Chrs 7 and 9 were unique to vertebrae. When the two bone sites had a QTL on the same chromosome, the same marker had the highest, although different, LOD score. A pairwise comparison by analysis of variance (ANOVA) did not reveal significant gene × gene interactions between QTLs for either bone site. BMD variance accounted for by individual QTLs ranged from 1% to 10%. Collectively, the BMD QTLs for femurs accounted for 35.1% and for vertebrae accounted for 23.7% of the F2 population variances in these bones. When mice were homozygous c3/c3 in the QTL region, 8 of the 10 QTLs increased, while the remaining two QTLs on Chrs 6 and 12 decreased, femoral BMD. Similarly, when mice were homozygous c3/c3 in the QTL region for the vertebrae, five of the seven QTLs increased, while two QTLs on Chrs 7 and 9 decreased, BMD. These findings show the genetic complexity of BMD with multiple genes participating in its regulation. Although 5 of the 12 QTLs are considered to be skeleton-wide loci and commonly affect both femurs and vertebrae, each of the bone sites also exhibited unique QTLs. Thus, the BMD phenotype can be partitioned into its genetic components and the effects of these loci on normal bone biology can be determined. Importantly, the BMD QTLs that we have identified are in regions of the mouse genome that have known human homology, and the QTLs will become useful experimental tools for mechanistic and therapeutic analyses of bone regulatory genes.
Usability Engineering von elektronischen Programmführern (EPGs) (Usability Engineering of Electronic Programme Guides (EPGs))
Authors: Elster Johanna , Huber Patrick
Published: April 2006

In diesem Beitrag werden elektronische Programmführer (EPGs) und ihre Bedeutung als Navigatoren für das interaktive Fernsehen vorgestellt. Neben einer Übersicht der verschiedenen Modelle werden der Nutzerhintergrund und daraus abgeleitete Anforderungen beschrieben. Diese stellen zusätzlich zu technischen Beschränkungen spezifische Herausforderungen an die Gestaltung von EPGs dar, die in einer Auswahl kritischer Usability-Aspekte beleuchtet werden.
aonDigital TV — iTV am Beispiel Telekom Austria (aonDigital TV — iTV at Telekom Austria)
Authors: Huemer Birgit
Published: April 2006

In diesem Praxisbericht wird die Entwicklung von interaktivem digitalem Fernsehen (iTV) in der Telekom Austria vorgestellt. Dabei zeigt der Bericht, wie mit zwei umfangreichen Usertests das Produkt verbessert werden konnte. Detaillierte Ergebnisse veranschaulichen, worauf die NutzerInnen in der Interaktion mit der grafischen Oberfläche und der Fernbedienung ihren Fokus legen, welche Schwierigkeiten in der Bedienung aufgetreten sind und wie in Folge das Design angepasst wurde, um eine qualitativ möglichst hohe Bedienbarkeit zu erreichen. Dieser Beitrag liefert einen Überblick über den Entwicklungsprozess und die wichtigsten Erkenntnisse aus den beiden Usability-Tests.
Reducing Complexity of Interaction with Advanced Bathroom Lighting at Home (Reduktion der Interaktionskomplexität bei hochentwickelten Badezimmerbeleuchtungssystemen für die Heimanwendung)
Authors: Lucero Andres , Lashina Tatiana , Terken Jacques
Published: April 2006

Developments in lighting technology provide a wide range of new opportunities for domestic use which have been demonstrated in several interior design projects. At the same time, available user interfaces providing full control over these systems are too cumbersome to use and are not acceptable for the majority of consumers. To reduce this complexity, we aimed at creating an intuitive user interface control for advanced multi-source lighting systems. Based on participatory design techniques, we invited end-users to help us design and evaluate the new interaction concept. In the final evaluation the user interface design was rated highly with regard to its perceived usefulness and “ease of use”. New designs for ad-vanced lighting systems should aim at user-friendly interfaces that make the transition from ordinary light switches to these new interfaces as simple and natural as possible.
Mobile Endgeräte: Einfache Alleskönner — ein Widerspruch? (Mobile Devices and Simplicity — a Contradiction?)
Authors: Leiner Ulrich , Krzonkalla Sonja
Published: April 2006

Mobiltelefone sind in den letzten Jahren funktionsüberbordende Alleskönner geworden. Gleichzeitig ist die Nutzerzahl rapide auf über 2 Milliarden Menschen gewachsen. Der Beitrag analysiert die sich daraus ergebende Vielfalt an Nutzungs-Szenarien und leitet spezielle Anforderungen an das User Interface Design ab. Er vergleicht Mobiltelefone mit anderen, weit verbreiteten elektronischen Geräten, wie z.B. PCs. Ausgehend von dem immer lauter werdenden Ruf nach Vereinfachung werden verschiedene Strategien der Vereinfachung untersucht, wie Verbesserung der Ein- und Ausgabemöglichkeiten, Flexibilisierung, Personalisierung und Methoden der Funktionsreduktion bzw. -fokussierung. Den Abschluss bilden Praxisbeispiele sowie eine Einschätzung wesentlicher Entwicklungstrends.
Innovative Interaktionskonzepte für Fahrer-Informations-Systeme (Innovative Interaction Concepts for Driver Information-Systems)
Authors: Preissner Olaf , Rößger Peter
Published: April 2006

Fahrer-Informations-Systeme (FIS) sind hochintegrierte elektronische Systeme, die im Fahrzeug dem Fahrer Möglichkeiten zu Information, Navigation, Kommunikation und Unterhaltung bieten. Bei der Gestaltung der Mensch-Maschine-Schnittstelle (MMS) dieser Systeme spielen Fähigkeiten, Erwartungen und Bedürfnisse der Nutzer die Hauptrolle. Ziel ist es, neben einer möglichst einfachen Benutzbarkeit, die Einhaltung sicherheitskritischer Parameter und die Schaf-fung eines attraktiven Erscheinungsbildes. Am Beispiel des 1DIN Radionavigationssystems Cascade von Harman Becker Automotive Systems werden Probleme, Prozesse, Lösungen und Perspektiven im Bereich der HMI Gestaltung von FIS dargestellt.
Design of Communication Interfaces Together with Family Members in interLiving (Kooperative Gestaltung von Kommunikationsschnittstellen mit Familienmitgliedern im Projekt interLiving)
Authors: Westerlund Bo
Published: April 2006

The paper describes the way in which family members were involved in a project which aimed at designing technology to enhance communication between family members of different generations between 1 and 76 years old. This called for the use of several different methods and techniques in order to get information and understanding of the persons' needs and desires. The paper also describes in greater detail how one of the prototypes was developed.

The approach was cooperative design with no specific technique or medium decided from the beginning. The researchers working in the project had different backgrounds, for example in ethnography, computer science, and industrial design. They closely worked together in the different activities. The paper concludes by discussing the approach and comparing it to other possible design processes.
Das Konzept eines Engineering Portals zur benutzerzentrierten Unterstützung der Anlagenplanung (The Concept of an Engineering Portal for the User-Centred Plant Engineering Support)
Authors: During Andre , Wittenberg Carsten , Berger Ulrich
Published: April 2006

Die Anlagenplanung ist durch eine stark verflochtene Organisations- und Informationsstruktur zwischen den vielen beteiligten Firmen geprägt. Die komplexen Beziehungen und Abhängigkeiten spiegeln sich in den wäh-rend der Projektierungsphase entstehenden Objekten und Dokumenten wieder, deren Inhalte – häufig bedingt durch die verzweigten Strukturen – vielfach redundant sind. Basis einer effizienten Projektierung muss deshalb die Informations- und Datendurchgängigkeit über den gesamten Projektierungsprozess hinweg und darüber hinaus auch in den späteren Phasen des Lebenszyklusses einer industriellen Anlage sein. In der hier vorgestellten Forschungsarbeit soll jedoch nicht versucht werden, die dafür notwendigen gewerkeübergreifenden Datenmodelle bzw. Objektstrukturen zu entwickeln, welche erst einen automatisierten und somit effizienten Datenaustausch ermöglichen. Vielmehr soll hier ein Portal-Konzept vorgestellt werden, wie ein optimiertes Informationsmanagement inklusive Datenaustausch aus der benutzerzentrierten Sicht eines Projekteurs aussehen könnte, d.h. wie Objekte, Objektzustände und Funktionen in einem Objektmanager optimal darge-stellt und genutzt werden können.
Environmental chemicals and thyroid function
Authors: Boas Malene , Feldt-Rasmussen Ulla , Skakkebæk Niels E , Main Katharina M
Published: April 2006

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic–pituitary–thyroid axis at different levels. Mechanisms of action may involve the sodium–iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans.
A pituitary carcinoma secreting TSH and prolactin: a non-secreting adenoma gone awry
Authors: Brown Rebecca L , Muzzafar Tariq , Wollman Robert , Weiss Roy E
Published: April 2006

To our knowledge, only one case of a TSH-secreting carcinoma has previously been reported. We describe here a second patient with a pituitary carcinoma producing TSH and prolactin (PRL). A 37-year-old male underwent a left frontotemporal craniotomy in 1996 for a sellar mass. Except for mildly increased PRL and elevated α-subunit, hormone evaluation was normal. Pathologic examination revealed a chromophobe adenoma with increased mitotic forms. The patient completed a course of external beam radiation to the pituitary and was prescribed l-thyroxine, bromocriptine, and hydrocortisone. He was lost to follow-up but did well for 6 years, until 2002, when he presented with TSH-dependent thyrotoxicosis and hyperprolactinemia. The patient was started on bromocriptine and propylthiouracil and was, again, lost to follow-up. In 2004, 9 years after his initial presentation, he presented after falling. Magnetic resonance imaging showed two brain masses with associated midline shift. Emergent resection of the larger mass revealed a pituitary cancer with positive staining for PRL, but not for TSH. Nine months later, the patient underwent further debulking of metastatic disease. Although development of a carcinoma from a pituitary adenoma is very rare (<0.5%), macroadenomas that become hormonally active should be suspect for transformation into pituitary cancer.
An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance
Authors: Rietveld I , Hofman A , Pols H A P , van Duijn C M , Lamberts S W J , Janssen J A M J L
Published: April 2006

Objective: Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects.

Design: We investigated whether a polymorphism near the promoter region of the IGF-I gene was related to the development of MA.

Methods: For this study, 1069 participants of the Rotterdam study were selected (440 participants with an abnormal glucose tolerance (AGT), 220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595 subjects with a normal glucose tolerance (NGT).

Results: 787 subjects were carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2–7.7); P = 0.02) in variant carriers with AGT than in carriers of the wild type of this IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2–4.0); P = 0.009). Compared with wild type carriers with AGT, the relative risk for MA was unadjusted and non-significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8–2.9). However, after adjustment for possible confounding factors (age, gender, mean blood pressure, fasting insulin, fasting glucose and smoking) this risk became significant (OR: RR 2.1; 95% CI:1.1–4.4; P = 0.04).

Conclusions: In subjects with AGT, a higher risk for MA was observed in variant carriers than in carriers of the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily associated with cardiovascular disease in subjects with AGT, our study suggests that variant carriers have a higher risk for cardiovascular disease than carriers of the wild type when they develop an AGT.
An alternative spliced variant of circulating soluble tumor necrosis factor-α receptor-2 is paradoxically associated with insulin action
Authors: Fernández-Real José Manuel , Straczkowski Marek , Lainez Begoña , Chacón Matilde R , Kowalska Irina , López-Bermejo Abel , García-España Antonio , Nikolajuk Agnieszka , Kinalska Ida , Ricart Wifredo
Published: April 2006

Objective: Serum concentrations of soluble tumor necrosis factor-α (TNF-α) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this circulating DS-TNFR2 is associated with insulin action in humans.

Design and methods: Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in monocytes. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Insulin sensitivity was measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model of assessment (HOMA) value in a replication study of 223 subjects.

Results: Real time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy subjects. A significant and positive association was found between serum DS-TNFR2 concentration and insulin sensitivity (P = 0.032, n = 76). This association was most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002). The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than those with undetectable DS-TNFR2 (42.12±22.08 vs 31.71± 16.95 μmol × kg−1 × min−1, P = 0.039). DS-TNFR2 was inversely associated with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting serum glucose, serum triglycerides and serum uric acid concentration and with the HOMA value (P = 0.03) in the replication study. Circulating DS-TNFR2 declined with increased number of components of the metabolic syndrome.

Conclusion: Native sTNFR2 and DS-TNFR2 show opposite associations with insulin action. DS-TNFR2 might play a role as a counterpart of the proinflammatory environment associated with insulin resistance.
Free fatty acids decrease circulating ghrelin concentrations in humans
Authors: Gormsen Lars C , Gjedsted Jakob , Gjedde Signe , Vestergaard Esben Thyssen , Christiansen Jens S , Jørgensen Jens Otto , Nielsen Søren , Møller Niels
Published: April 2006

Objective: Concentrations of the orexigenic peptide ghrelin is affected by a number of hormones, which also affect circulating levels of free fatty acids (FFAs). The present study was therefore designed to determine the direct effect of FFAs on circulating ghrelin.

Design: Eight lean, healthy men were examined for 8 h on four occasions using variable infusion rates (0, 3, 6 and 12 μl/kg per min) of intralipid to create different plasma FFA concentrations. Constant levels of insulin and GH were obtained by administration of acipimox (250 mg) and somatostatin (300 μg/h). At the end of each study day a hyperinsulinaemic-euglycaemic clamp was performed.

Results: Four distinct levels of FFAs were obtained at the end of the lipid infusion period (FFALIPID: 0.03 ± 0.00 vs: 0.49 ± 0.04, 0.92 ± 0.08 and 2.09 ± 0.38 mmol/l; ANOVA P < 0.0001) and during hyperinsulinaemia (FFALIPID+INSULIN: 0.02 ± 0.00 vs: 0.34 ± 0.03, 0.68 ± 0.09 and 1.78 ± 0.32 mmol/l; ANOVA P < 0.0001). Whereas, somatostatin infusion alone reduced ghrelin concentration by ~67%, concomitant administration of increasing amounts of intralipid reduced circulating ghrelin by a further 14, 19 and 19% respectively (change in ghrelin: 0.52 ± 0.05 vs: 0.62 ± 0.06, 0.72 ± 0.09 and 0.71 ± 0.05 μg/l; ANOVA P = 0.04). No further reduction in ghrelin concentration was observed during hyperinsulinaemia.

Conclusion: FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin levels independent of ambient GH and insulin levels.
High-dose glucocorticoids increase serum levels of soluble IL-6 receptor α and its ratio to soluble gp130: an additional mechanism for early increased bone resorption
Authors: Dovio Andrea , Perazzolo Laura , Saba Laura , Termine Angela , Capobianco Marco , Bertolotto Antonio , Angeli Alberto
Published: April 2006

Objective: Glucocorticoids (GCs) at pharmacological doses stimulate bone resorption. Mechanisms of this action are unclear. The osteoclastogenic cytokine interleukin (IL)-6 acts through an oligomeric receptor consisting of two subunits, gp80 (or IL-6 receptor α, IL-6Rα) and gp130; both exist in membrane and soluble forms. Soluble IL-6Rα (sIL-6Rα) enhances, while sgp130 inhibits IL-6 signalling. In vitro, GCs enhance many effects of IL-6 by up-regulation of IL-6Rα. The aim of the present study was to assess acute changes of IL-6 system in the peripheral blood of patients given high-dose GCs.

Subjects and methods: Serum levels of IL-6, sIL-6Rα, sgp130 and bone turnover markers were assessed before and each day during treatment in 24 multiple sclerosis (MS) patients undergoing high-dose (prednisolone, 15 mg/kg per day), short-term (3 to 5 days) intravenous GC therapy for relapse at the Regional Multiple Sclerosis Centre.

Results: An immediate and marked fall of osteocalcin and an early increase of C-terminal telopeptide of type I collagen were already noticed at day 2 (P < 0.001 and P < 0.02, respectively); both became more apparent in the subsequent days. IL-6 was always below or near the detection limit of our ELISA. sgp130 showed a slight increase. sIL-6Rα significantly increased, peaking at day 4 (P < 0.01). However, inter-individual variability of response was noticed. Four patients showed a slight decrease, while no change was observed in one patient and an increase was noticed in the remaining nineteen (maximum change ranging from +10% to +67% with respect to baseline). In these patients, a significant increase of sIL-6Rα/sgp130 ratio was apparent. No correlation was found between bone turnover markers and any measured component of the IL-6 system.

Conclusions: sIL-6Rα and sIL-6Rα/sgp130 ratio are precociously increased in the peripheral blood of the vast majority of patients given high-dose, intravenous GCs. The increase of systemically available sIL-6Rα conceivably results in the enhancement of IL-6-dependent osteoclastogenesis. The role of such a mechanism in the bone loss observed in inflammatory and immune-mediated diseases (where abundancy of IL-6 in the bone microenvironment is expected) requires further investigation.
Overview of Theoretical and Computational Methods Applied to the Oxygen‐Organic Molecule Photosystem
Authors: Paterson Martin J. , Christiansen Ove , Jensen Frank , Ogilby Peter R.
Published: April 2006

The challenges of using modern theoretical and computational tools to model the unique features of the oxygen‐organic molecule photosystem are discussed from a historical and pedagogical perspective. This review is written for the novice, but the problems formulated should stimulate the expert.
In Vitro Characteristics and In Vivo Immunosuppressive Activity of Compact Bone-Derived Murine Mesenchymal Progenitor Cells
Authors: Guo Zikuan , Li Hong , Li Xiusen , Yu Xiaodan , Wang Hengxiang , Tang Peihsien , Mao Ning
Published: April 2006

In contrast to the considerable amount of data that documents the biological properties of mesenchymal progenitor cells from human and other species, there is still paucity of information about mouse counterparts, as their purification and culture expansion procedures remain rudimentary. In the present study, murine mesenchymal progenitor cell (muMPC) culture was developed by explant culture of collagenase-digested bone fragments after removal of the released cells. During cultivation, fibroblastoid cells sprouted and migrated from the fragments, followed by adherent monolayer development. The cells exhibited homogenous surface antigen profile and presented in vitro multipotential differentiation along osteocyte, chondrocyte, and adipocyte lineages, as evaluated by matched cell or matrix staining and reverse transcription polymerase chain reaction techniques. Also, the surface antigenic epitope changed and potential of proliferation and multidifferentiation decreased with successive subculturing. Functional investigations demonstrated that these cells supported in vitro hematopoiesis and suppressed lymphocyte cell proliferation triggered by ConA or allogeneic splenocytes. Furthermore, muMPCs prolonged the mean survival time of skin grafts across the major histocompatibility barrier (H2b → H2d), suggestive of the immunosuppressive effects in vivo. The findings demonstrate that muMPCs obtained with this simple protocol are similar in property to their marrow counterparts, and thus, the protocol described here could be used for further investigations in mouse physiological and pathological models.
Effects of a Waste Paper Product on Soil Phosphorus, Carbon, and Bulk Density
Authors: Brauer David , Aiken Glen
Published: April 2006

Applications of manures to agricultural fields have increased soil test values for P to high levels in parts of the USA and thus increased the likelihood that P will be transported to surface water and degrade its quality. Waste paper applications to soils with high STP (soil test P) may decrease the risk of P transport to surface water by decreasing DRP (dissolved reactive P) by the formation of insoluble Al–P complexes and providing organic matter to improve infiltration. A field experiment was conducted near Booneville, AR (USA) to assess the effects of different rates of a waste paper product addition on STP, soil bulk density, and total soil C with a soil with approximately 45 mg Bray1‐P kg−1 soil (dry weight). A Leadvale silt loam soil (fine‐silty, siliceous, thermic Typic Fragiudult) was amended with 0, 22, 44, or 88 Mg waste paper product ha−1 to supply approximately 90, 170, or 350 kg Al ha−1, respectively. One year after additions, there was a strong negative correlation between waste paper product application rates and soil bulk density, and a strong positive correlation between rates and total soil C content. Soil bulk density and total C 2 yr after additions, and soil DRP and Bray1‐P were not affected by waste paper additions. These results support the hypothesis that decreases in DRP in runoff from soils receiving waste paper additions were probably due to changes in soil organic matter and bulk density, rather than changes in the chemical forms of soil P.
Identifying Sources of Fecal Contamination Inexpensively with Targeted Sampling and Bacterial Source Tracking
Authors: McDonald Jennifer L. , Hartel Peter G. , Gentit Lisa C. , Belcher Carolyn N. , Gates Keith W. , Rodgers Karen , Fisher Jared A. , Smith Katy A. , Payne Karen A.
Published: April 2006

Most bacterial source tracking (BST) methods are too expensive for most communities to afford. We developed targeted sampling as a prelude to BST to reduce these costs. We combined targeted sampling with three inexpensive BST methods, Enterococcus speciation, detection of the esp gene, and fluorometry, to confirm the sources of fecal contamination to beaches on Georgia's Jekyll and Sea Islands during calm and stormy weather conditions. For Jekyll Island, the most likely source of contamination was bird feces because the percentage of Ent. faecalis was high (30%) and the esp gene was not detected. For the Sea Island beach during calm conditions, the most likely sources of fecal contamination were leaking sewer lines and wildlife feces. The leaking sewer lines were confirmed with fluorometry and detection of the esp gene. For the Sea Island beach during stormflow conditions, the most likely sources of fecal contamination were wildlife feces and runoff discharging from two county‐maintained pipes. For the pipes, the most likely source of contamination was bird feces because the percentage of Ent. faecalis was high (30%) and the esp gene was not detected. Sediments were also a reservoir of fecal enterococci for both Jekyll and Sea Islands. Combining targeted sampling with two or more BST methods identified sources of fecal contamination quickly, easily, and inexpensively. This combination was the first time targeted sampling was conducted during stormy conditions, and the first time targeted sampling was combined with enterococcal speciation, detection of the esp gene, and fluorometry.
Predicting Phosphorus Availability from Soil‐Applied Composted and Non‐Composted Cattle Feedlot Manure
Authors: Zvomuya Francis , Helgason Bobbi L. , Larney Francis J. , Janzen H. Henry , Akinremi Olalekan O. , Olson Barry M.
Published: April 2006

Prediction of phosphorus (P) availability from soil‐applied composts and manure is important for agronomic and environmental reasons. This study utilized chemical properties of eight composted and two non‐composted beef cattle (Bos taurus) manures to predict cumulative phosphorus uptake (CPU) during a 363‐d controlled environment chamber bioassay. Ten growth cycles of canola (Brassica napus L.) were raised in pots containing 2 kg of a Dark Brown Chernozemic clay loam soil (fine‐loamy, mixed, Typic Haploboroll) mixed with 0.04 kg of the amendments. Inorganic P fertilizer (KH2PO4) and an unamended control were included for comparison. All treatments received a nutrient solution containing an adequate supply of all essential nutrients, except P, which was supplied by the amendments. Cumulative P uptake was similar for composted (74 mg kg−1 soil) and non‐composted manures (60 mg kg−1 soil) and for the latter and the fertilizer (40 mg kg−1 soil). However, the CPU was significantly higher for organic amendments than the control (24 mg kg−1 soil) and for composted manure than the fertilizer. Apparent phosphorus recovery (APR) from composted manure (24%) was significantly lower than that from non‐composted manure (33%), but there was no significant difference in APR between the organic amendments and the fertilizer (27%). Partial least squares (PLS) regression indicated that only two parameters [total water‐extractable phosphorus () and total phosphorus (TP) concentration of amendments] were adequate to model amendment‐derived cumulative phosphorus uptake (ACPU), explaining 81% of the variation in ACPU. These results suggest that P availability from soil‐applied composted and non‐composted manures can be adequately predicted from a few simple amendment chemical measurements. Accurate prediction of P availability and plant P recovery may help tailor manure and compost applications to plant needs and minimize the buildup of bioavailable P, which can contribute to eutrophication of sensitive aquatic systems.
Engaging spirituality in the transformative higher education classroom
Authors: Tolliver Derise E. , Tisdell Elizabeth J.
Published: April 2006

This chapter discusses the challenges of fostering spirituality in the higher education classroom and its relationship to the practice of transformative learning.
Using fiction for transformation
Authors: Jarvis Christine
Published: April 2006

This chapter examines how the study of popular romantic fiction was used to transform students' understandings of the ways in which gendered identities are constructed and their perception of the way textual meanings are determined.
Do the write thing
Authors: Burk Adrienne L.
Published: April 2006

This chapter describes an innovative writing program at Simon Fraser University that has implications for fostering transformative learning.
The challenge of teaching for change
Authors: Taylor Edward W.
Published: April 2006

In summarizing the shared themes of the authors of the previous chapters, this chapter explores the role of the transformative educator, the transformative classroom environment, the transformative text, and the student when teaching for change.
WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH
Authors: Lennon P.A. , Scott D.A. , Lonsdorf D. , Wargowski D.S. , Kirkpatrick S. , Patel A. , Cheung S.W.
Published: April 2006

Aniridia usually occurs in isolation, but may also occur as part of the WAGR contiguous gene deletion syndrome, which includes Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. The aniridia and predisposition for Wilms tumor seen in WAGR are caused by haploinsufficiency for PAX 6 and WT1, respectively. We present a female infant with aniridia, bilateral ptosis, bilateral posterior capsular cataracts, nystagmus, left‐sided glaucoma, microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor delay consistent with a clinical diagnosis of WAGR syndrome. In addition, weight‐for‐height ratio at 12 months is at the 94th centile, raising the possibility of a diagnosis of WAGRO (WAGR + Obesity). Chromosome analysis revealed a translocation (11;15)(p13;p11.2) which has not been previously associated with a diagnosis of WAGR. Subsequent clinical WAGR fluorescent in situ hybridization (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A complete FISH‐mapping of the breakpoints on chromosome 11 revealed a 7 Mb deletion within 11p13–11p14. The patient is examined in light of other reported patients with deletions and/or translocations involving the regions between 11p12 → 11p14 including patients with WAGR + obesity (WAGRO) as well as with other reported patients with aniridia and congenital ptosis. © 2006 Wiley‐Liss, Inc.
Titelbild: Proteolytic Actuation of Nanoparticle Self‐Assembly (Angew. Chem. 19/2006)
Authors: Harris Todd J. , von Maltzahn Geoffrey , Derfus Austin M. , Ruoslahti Erkki , Bhatia Sangeeta N.
Published: April 2006

Durch Proteasen ausgelöste Nanopartikelselbstorganisation diente zum Aufbau multimerer Assoziate mit neuen Eigenschaften. In ihrer Zuschrift auf S. 3233 ff. zeigen S. N. Bhatia et al., dass das Binden komplementärer Fe3O4‐Nanopartikel durch das Anbinden von Polymeren inhibiert wird. Das Nanopartikel bleibt in seinem “Ruhezustand”, bis eine Protease seine Selbstorganisation auslöst.
Eudragit S (methyl methacrylate methacrylic acid copolymer)/fatty acid blends as form‐stable phase change material for latent heat thermal energy storage
Authors: Sari Ahmet , Alkan Cemil , Kolemen Ugur , Uzun Orhan
Published: April 2006

By composing (Eudragit S) with fatty acids (stearic acid (SA), palmitic acid (PA), and myristic acid (MA)), form‐stable phase change materials (PCMs), which can retain the same shape in a solid state even when the temperature of the PCMs is over the melting points of the fatty acids, are prepared. The compatibility of fatty acids with the Eudragit S is proved by microscopic investigation and infrared (FTIR) spectroscopy. The melting and crystallization temperatures and the latent heats of melting and crystallization of the form‐stable PCMs are measured by Differential Scanning Calorimetry (DSC) method. The maximum mass percentage of all fatty acids in the form‐stable PCMs is found as 70%, and no leakage of fatty acid is observed at the temperature range of 50–70°C for several heating cycles. Thermal properties obtained from the DSC analysis indicate that the Eudragit S/fatty acid blends as form‐stable PCM have great potential for passive solar latent heat thermal energy storage (LHTES) applications in terms of their satisfactory thermal properties and utility advantage. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1402–1406, 2006
The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis
Authors: Kirwan John R. , Hickey Sarah H. , Hällgren Roger , Mielants Herman , Björck Ewa , Persson Tore , Wollheim Frank A.
Published: April 2006

Objective

To measure the effect of low‐dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA).

Methods

Patients with RA who took part in a randomized double‐blind placebo‐controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60‐minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3‐month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients.

Results

Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30‐minute and 60‐minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria.

Conclusion

Low doses of a glucocorticoid resulted in depression of baseline and ACTH‐stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic–pituitary–adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further.
A novel role for suppressor of cytokine signaling 3 in cartilage destruction via induction of chondrocyte desensitization toward insulin‐like growth factor
Authors: Smeets R. L. , Veenbergen S. , Arntz O. J. , Bennink M. B. , Joosten L. A. B. , van den Berg W. B. , van de Loo F. A. J.
Published: April 2006

Objective

An important mechanism contributing to cartilage destruction in arthritis is chondrocyte desensitization toward its main anabolic factor, insulin‐like growth factor 1 (IGF‐1). In this study, we sought to determine the role of suppressor of cytokine signaling 3 (SOCS‐3) in the induction of IGF‐1 desensitization of murine chondrocytes.

Methods

Chondrocyte responsiveness to IGF‐1 was assessed by 35S‐sulfate incorporation into proteoglycans (PGs), via aggrecan messenger RNA expression, using quantitative real‐time polymerase chain reaction or insulin receptor substrate 1 (IRS‐1) tyrosine phosphorylation (Western blot analysis). IGF‐1 desensitization of patellar chondrocytes was studied in zymosan‐induced arthritis. IGF‐1 desensitization was induced in patellar cartilage explants or the H4 chondrocyte cell line, exposed to interleukin‐1α (IL‐1α). SOCS‐3 protein expression was assessed by immunohistochemistry or by Western blot analysis of protein extracts. The role of SOCS‐3 in IGF‐1 signaling was elucidated by adenoviral overexpression.

Results

Exposure of murine articular cartilage to IL‐1 caused a significant decrease in IGF‐1–induced PG synthesis. This effect also occurred in inducible nitric oxide synthase–knockout mice, revealing the involvement of a secondary IL‐1–induced factor other than nitric oxide. We showed that IL‐1 significantly up‐regulated SOCS‐3 transcription and protein synthesis in H4 chondrocytes. In contrast, IL‐18 was unable to induce SOCS‐3 expression and failed to induce chondrocyte IGF‐1 desensitization. Histologic analysis of samples from arthritic knee joints revealed high expression of SOCS‐3 in chondrocytes. Through adenoviral overexpression of SOCS‐3, we obtained direct evidence that SOCS‐3 inhibits IGF‐1–mediated cell signaling, since IRS‐1 phosphorylation was reduced.

Conclusion

This study demonstrates that IL‐1–induced SOCS‐3 expression is a novel mechanism of IGF‐1 desensitization in chondrocytes; in conjunction with nitric oxide it can contribute to cartilage damage during arthritis.
Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis
Authors: Makrygiannakis Dimitrios , af Klint Erik , Catrina Sergiu‐Bogdan , Botusan Ileana Ruxandra , Klareskog Elin , Klareskog Lars , Ulfgren Ann‐Kristin , Catrina Anca Irinel
Published: April 2006

Objective

Intraarticular corticosteroids are frequently used as successful adjuvant therapy for inflammatory arthritides, but little is known about their effects on molecules that regulate bone biology. We undertook this study to investigate the effect of intraarticular corticosteroids on the synovial expression of RANKL and osteoprotegerin (OPG).

Methods

We evaluated RANKL, OPG, and surface marker expression by immunohistochemical methods in synovial knee biopsy samples obtained from 13 patients with inflammatory arthritis before and 2 weeks following intraarticular injection of triamcinolone hexacetonide. We further investigated the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL and OPG expression in osteoblast‐like cells, by Western blotting.

Results

Intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages, evaluated as both CD68+ and CD163+ cells. This change was paralleled by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL:OPG ratio. DEX down‐regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro pretreatment of osteoblast‐like cells with tumor necrosis factor favored an antiresorptive effect of DEX treatment through a similar down‐regulation of RANKL expression.

Conclusion

The decrease in inflammation attributed to intraarticular corticosteroids is accompanied by down‐modulation of bone destruction markers. These findings offer a rationale for the beneficial effect of corticosteroids on joint erosion in arthritis.
Fas activation of a proinflammatory program in rheumatoid synoviocytes and its regulation by FLIP and caspase 8 signaling
Authors: Palao Guillermo , Santiago Begoña , Galindo Marı´a , Rullas Joaquı´n , Alcamı´ José , Ramirez Juan C. , Pablos José L.
Published: April 2006

Objective

The expansion of an aggressive population of fibroblast‐like synoviocytes (FLS) in rheumatoid arthritis (RA) synovium occurs despite their expression of functional death receptors and exposure to death receptor ligands. FLS can survive Fas challenge because of the constitutive expression of FLIP apoptosis inhibitor. We investigated whether Fas signaling plays a pathogenetic role by activating a nonapoptotic proinflammatory program in RA FLS.

Methods

Cultured RA FLS were stimulated with an agonistic anti‐Fas antibody in the presence or absence of the caspase inhibitor Z‐VAD‐FMK or after RNA interference with a short hairpin RNA expression plasmid directed against FLIP. NF‐κB and activator protein 1 (AP‐1) activation was studied by electrophoretic mobility shift assays and p65 immunofluorescence analysis, and expression of messenger RNA (mRNA) for monocyte chemoattractant protein 1, interleukin‐8, IκBα, and matrix metalloproteinases (MMPs) 1, 9, and 13 was examined by reverse transcription–polymerase chain reaction. Chemotactic activity of Fas‐activated FLS–conditioned media was studied in Transwell migration assays.

Results

Fas stimulation activated NF‐κB and AP‐1, and this response required caspase activity, since Z‐VAD‐FMK inhibitor precluded it. FLIP was processed to p43 protein after Fas stimulation in a caspase‐dependent manner, and inhibition of FLIP expression resulted in reduced Fas‐triggered NF‐κB activation. Fas stimulation increased expression of mRNA for IκBα, MMPs, and chemokines, and Fas‐activated RA FLS displayed increased chemotactic activity for monocytic cells.

Conclusion

Fas triggering may contribute to the proinflammatory features of RA FLS by activating NF‐κB and AP‐1 and by expression of relevant target genes, such as MMPs and chemokines. Fas proinflammatory signaling is dependent upon caspase activity and FLIP expression. These data implicate FLIP as a potentially important molecular switch that turns the Fas signaling away from apoptosis and toward induction of a proinflammatory phenotype in RA FLS.
Development of a preliminary index that predicts adverse events after total knee replacement
Authors: Solomon Daniel H. , Chibnik Lori B. , Losina Elena , Huang Jenny , Fossel Anne H. , Husni Elaine , Katz Jeffrey N.
Published: April 2006

Objective

We undertook this study to assess the relationships between hospital characteristics, volume of procedures, and perioperative outcomes after total knee replacement (TKR), and to use this information to construct a simple predictive index for perioperative outcomes that incorporates hospital‐ and patient‐level characteristics.

Methods

We studied Medicare beneficiaries who underwent TKR in 4 US states in 2000. Orthopedic surgery administrators from hospitals caring for patients in this sample were surveyed about a range of hospital characteristics. The relationships between these hospital characteristics, patient variables, and 90‐day postoperative adverse events (including death, pulmonary embolus, pneumonia, deep wound infection, and acute myocardial infarction) were assessed using generalized estimating equations adjusting for hospital volume. These relationships were assessed in low‐ and high‐risk patient groups. Variables from the final multivariate model were used to create an index that was tested against 90‐day adverse event rates.

Results

Three hundred twenty‐seven (3.6%) of the patients undergoing TKR in our sample experienced an adverse event. In the final multivariate regression models, variables that predicted adverse perioperative events included low hospital volume (fewer than 23 TKRs in the Medicare population per year), absence of a preoperative teaching program, fewer TKRs conducted in a dedicated orthopedic surgery operating room, patient age >70 years, male sex, and at least 1 comorbid condition. The effect of volume on perioperative adverse events was evident both in patients with few risk factors and in patients with several risk factors. An index including the 6 patient and hospital variables discriminated well, with adverse events occurring in 2.0% (95% confidence interval [95% CI] 1.4–2.7%) of patients in the lowest risk category and in 7.4% (95% CI 4.5–12.3%) of patients in the highest risk category (P for trend < 0.001). The index predicted adverse event rates both in hospitals with a low volume of TKRs and in those with a high volume of TKRs.

Conclusion

Characteristics of hospital care, procedure volume, and patient‐level factors are all associated with perioperative outcomes of TKR. A preliminary index combining hospital characteristics and volume is moderately predictive of adverse perioperative outcomes. The index is predictive of outcome in low‐ and high‐volume hospitals.
Mediation of endothelial cell damage by serine proteases, but not superoxide, released from antineutrophil cytoplasmic antibody–stimulated neutrophils
Authors: Lu X. , Garfield A. , Rainger G. E. , Savage C. O. S. , Nash G. B.
Published: April 2006

Objective

To evaluate potential mediators of endothelial cell injury in systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs), we investigated the factors controlling the neutrophil respiratory burst and endothelial release of von Willebrand factor (vWF) during neutrophil–endothelial cell interactions.

Methods

Superoxide release from neutrophils binding to purified P‐selectin or to tumor necrosis factor–activated endothelial cells was measured under flow or static conditions using the superoxide dismutase (SOD)–inhibitable reduction of ferricytochrome c. Neutrophils were activated with fMLP, normal IgG, or ANCA IgG. Enzyme‐linked immunosorbent assay was used to measure vWF. Serine protease activity was measured enzymatically.

Results

ANCA IgG or fMLP induced superoxide release when perfused over neutrophils that were rolling over P‐selectin, but not those that were binding to endothelial cells. In static assays, endothelial cells inhibited superoxide production by neutrophils. Adenosine inhibited the respiratory burst, and, in cocultures, adenosine deaminase overcame the inhibitory effects of endothelial cells. Serine proteases were released during activated neutrophil–endothelial cell coculture. There was enhanced release of vWF during activated neutrophil–endothelial cell coculture; this was not inhibited by diphenyleneiodonium or by SOD plus catalase, but was inhibited by diisopropylfluorophosphate.

Conclusion

Endothelial cells inhibit superoxide generation by fMLP and ANCA‐activated neutrophils. The release of vWF occurs during coculture and is sensitive to serine protease, but not NADPH oxidase inhibition. Serine proteases may play a more important role than reactive oxygen species as mediators of endothelial injury during ANCA‐associated systemic vasculitis.