bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Effectiveness of the Massachusetts Workforce Development System Using No-Shows as a Nonexperimental Comparison Group
Authors: Raphael Steven , Stoll Michael A.
Published: June 2006

This article examines the effect of the Massachusetts workforce development system on the earnings of disadvantaged adults using nonexperimental data from the late 1990s. The authors construct a comparison sample for program participants using individuals who apply for and are offered services yet do not participate in a training program. They present a series of difference-in-difference estimates that make several alternative efforts to correct for selectivity bias, including econometric models that regression adjust for observable characteristics and fixed-effect models that adjust for time-invariant person effects. They also employ probabilistic matching techniques to more finely align the treatment and comparison samples. On average, program participants experienced 20% increases in annual earnings 1 year postintervention and 25% increases after 2 years. The authors uncover considerable heterogeneity in these effects, suggesting that the most difficult to serve and the most job ready benefit the least.
The Imprecise Science of Evaluating Scholarly Performance
Authors: Lange Thomas
Published: June 2006

In a growing number of countries, government-appointed assessment panels develop ranks on the basis of the quality of scholarly outputs to apportion budgets in recognition of evaluated performance and to justify public funds for future R&D activities. When business and management journals are being grouped in broad quality categories, a recent study has noted that this procedure was placing the same journals in essentially the same categories. Drawing on journal quality categorizations by several German- and English-speaking business departments and academic associations, the author performs nonparametric tests and correlations to analyze whether this claim can be substantiated. In particular, he examines the ability of broad quality categorizations to add value to governmental, administrative, and academic decision making by withstanding the criticism traditionally levied at research quality assessments.
How to Begin a New Topic in Mathematics
Authors: Ma Xin , Papanastasiou Constantinos
Published: June 2006

The authors use Canadian data from the Third International Mathematics and Science Study to examine six instructional methods that mathematics teachers use to introduce new topics in mathematics on performance of eighth-grade students in six mathematical areas (mathematics as a whole, algebra, data analysis, fraction, geometry, and measurement). Results of multilevel analysis with students nested within schools show that the instructional methods of having the teacher explain the rules and definitions and looking at the textbook while the teacher talks about it had little instructional effects on student performance in any mathematical area. In contrast, the instructional method in which teachers try to solve an example related to the new topic was effective in promoting student performance across all mathematical areas.
Evaluation of Curricula in Higher Education
Authors: Spiel Christiane , Schober Barbara , Reimann Ralph
Published: June 2006

Evaluation of teaching at universities is traditionally realized in terms of student ratings. Curriculum evaluation is rarely done in a systematic manner. More often, the emphasis is placed on a particular aspect, which is only of little help in terms of modifying education. A very prominent example is that of medical education. Here, evaluations of curricula primarily focus on new curricula by contrasting them to traditional ones. The article at hand deals with a different evaluation approach, in which five phases have to be considered and contrasting results to other teaching formats are not the main focus. In this article, the authors concentrate on the first phase (baseline evaluation) of the systematic evaluation of a medical curriculum. They describe several challenges of such an evaluation approach and illustrate the strategies used to overcome them. In addition, associated relevant empirical findings from this evaluation study are presented.
Towards a Faith-Based Program Theory
Authors: Harden Mark G.
Published: June 2006

A meta-program theory is proposed to overcome the limitations and improve the use of program theory as an approach to faith-based program evaluation. The essentials for understanding religious organizations, their various programs, and faith and spirituality are discussed to support a rationale for developing a faith-based program theory that captures the complex nature of religious program phenomena. Implications for public policy are examined. New concepts based on structural approach and four program theories are formulated for program analysis. Several theoretical concepts for faith-based program evaluation to guide methods for describing patterns that reflect the religious beliefs and values are suggested.
Creativity and flow in musical composition: an empirical investigation
Authors: MacDonald Raymond , Byrne Charles , Carlton Lana
Published: June 2006

Although an extensive literature exists on creativity and music, there is a lack of published research investigating possible links between musical creativity and Csikszentmihalyi's concept of flow or optimal experience. This article examines a group composition task to study the relationships between creativity, flow and the quality of the compositions produced. First-year university students ( n = 45) worked on a group composition task during three meetings. Each time the students met, they completed a detailed questionnaire that assessed aspects of each student's experience of the group compositional process using an ‘experience sampling form’ based on Csikszentmihalyi's previous work. Completed compositions were recorded and rated for quality and creativity by the participants and by a group of music education specialists ( n= 24). Results indicated a number of ways in which the specialists’ assessments of quality related to the students’ assessments of creativity and flow. The study provides an example of a research method that can be used to further our understanding of the processes and outcomes of group music composition tasks. The discussion also considers a number of important ways that the concept of flow can be utilized within a music education context.
An empirical investigation of creativity and musical experience
Authors: Goncy Elizabeth A. , Waehler Charles A.
Published: June 2006

This preliminary investigation examined the relationship between creative personality traits and musical experience. Creative personality traits were hypothesized to be positively correlated with musical experience. Two self-report measures, the Creative Personality Scale and the Scale of Musical Experience, were designed for this study. Initial analyses showed that both measures designed for this study were reliable and valid. Students ( n = 150) from Introduction to Psychology and Music classes participated in the study. Results from correlational analyses showed that there was a positive correlation ( r = .34, p < .01) between creative personality traits and musical experiences.
Perceived complexity of western and African folk melodies by western and African listeners
Authors: Eerola Tuomas , Himberg Tommi , Toiviainen Petri , Louhivuori Jukka
Published: June 2006

Stylistic knowledge and enculturation play a significant role in music perception, although the importance of psychophysical cues in perception of emotions in music has been acknowledged. The psychophysical cues, such as melodic complexity, are assumed to be independent of musical experience. A cross-cultural comparison was used to investigate the ratings of melodic complexity of western and African participants for western (Experiment 1) and African folk songs (Experiment 2). A range of melodic complexity measures was developed to discover what factors contribute to complexity. On the whole, the groups gave similar patterns of responses in both experiments. In Experiment 1, western folk songs represented a style that was familiar for both groups and the results portrayed the differences in stylistic knowledge and high predictive rate of melodic variables. In Experiment 2, African folk songs were stylistically familiar only for the African group and the results illustrated a lower predictive rate of variables and differences between the groups in rhythm and structural variables. These results suggest that the melodic complexity ratings are influenced by musical enculturation.
Response To Bettie St.Pierre’s “Scientifically Based Research in Education: Epistemology and Ethics”
Authors: Feuer Michael J.
Published: June 2006

In this brief rejoinder to Professor St.Pierre, the author focuses on two points: the purposes, origins, and role of the National Academy of Sciences (and its constituent units); and the importance of rigorous evidence in the pursuit of education policy and reform.
Scientifically Based Research in Education: Epistemology and Ethics
Authors: St.Pierre Elizabeth Adams
Published: June 2006

In this article, the author begins to trace the concept scientifically based research in federal legislation, in the Department of Education’s Institute of Education Sciences, and in the reports of several National Research Council committees. She also discusses how this concept has produced a certain scientism that has been deployed to attempt to control the field of educational research. She points out, however, that scientifically based research treats methodology as if it can be separated from epistemology and thus forgets that different bodies of knowledge and thought make different sciences possible. Thus, science is not one thing, as those who support scientifically based research often claim. Finally, the author suggests that our task as education scholars, researchers, and policy makers in this age of accountability is to engage rather than exclude epistemologies not our own that may help us produce different knowledge and produce knowledge differently.
Becoming a ‘woman to the backbone’
Authors: Jantzen Christian , Østergaard Per , Vieira Carla M. Sucena
Published: June 2006

The connection between consumption and identity construction is a well-known topic in consumer research.Identity has two sides: a social side directed towards an external world of shared values and symbols, and an intra-psychological side directed towards an internal world of longings and bodily sensations.In this study we investigate how women's consumption of lingerie may enhance their experience of inter- and intra-psychological identity.This process of identity formation is analysed with reference to Foucault's concept of ‘technologies of the self’which emphasizes the role of practices and instruments in generating a sense of ‘self’.Lingerie is treated as such an instrument, and the categorizations that consumers use are treated as a form of practical knowledge of how to determine the‘right’underwear for the‘right’occasion. Consuming lingerie with the purpose of experiencing feminine identity is a matter of controlling your bodily performance in social life.This working on identity by purchasing and wearing lingerie may furthermore fulfil or generate longings, thus potentially leading to intensified experiences, feelings and sensations of ‘who I really am’.The article highlights some of the paradoxes in this attempt to manage identity.The analysis is based on interviews with 22 women about their underwear and lingerie consumption.
Domestic dinner
Authors: Bugge Annechen Bahr , Almås Reidar
Published: June 2006

The purpose of this article is to explore contemporary representations and practices of the domestic dinner in the context of households in the process of establishing themselves and families in suburban Norway. The concept of a ‘proper dinner’ is the result of complex social and cultural processes. Cooking dinner is not only an act of caring for others, preparing a proper meal is also an act of positioning oneself. Cooking dinner is an important part of the symbolic production of socially and culturally acceptable feminine subject positions. The empirical analysis is based on in-depth interviews with 25 mothers of young children about how they think and act in their everyday dinner practice. The material shows clear limitations on individuality when it comes to dinner patterns. There is a network of social and cultural conventions that frame eating practices and distinguish between different dishes. These distinctions follow a clear temporal and spatial order. Dishes prepared from a common Norwegian ingredient, minced-meat, are used as an example of how dishes carry quite different social and cultural meanings.While there are several discourses surrounding dinner that offer different possibilities for action, some representations and practices are more ‘proper’ than others. Three distinct dinner models for proper meals are identified: the traditional, the trendy and the therapeutic.
Consumer tactics as ‘weapons’
Authors: Wiedenhoft Wendy A.
Published: June 2006

This article examines the role consumer tactics played in the American Federation of Labor's (AFL) strategy of business unionism. In particular, it explains how the AFL used its consumer tactics to try to mobilize the purchasing power of union members and their families to fight for higher wages and shorter working hours. The historical data collected for this article demonstrates that the AFL was not ignorant of the relationship between production and consumption, or the worker and the consumer. I discuss how the AFL used its consumer tactics to try to build solidarity across its affiliated trade unions and provide a way for the wives, daughters, and mothers of union men to become involved in the labor movement through consumption. I argue that these consumer tactics need to be fully acknowledged, as they were pivotal in some of the most contentious struggles between the AFL and business at the turn of the 20th century.
Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia
Authors: Ancliff Phil J. , Blundell Michael P. , Cory Giles O. , Calle Yolanda , Worth Austen , Kempski Helena , Burns Siobhan , Jones Gareth E. , Sinclair Jo , Kinnon Christine , Hann Ian M. , Gale Rosemary E. , Linch David C. , Thrasher Adrian J.
Published: June 2006

Severe congenital neutropenia (SCN) is characterized by neutropenia, recurrent bacterial infections, and maturation arrest in the bone marrow. Although many cases have mutations in the ELA2 gene encoding neutrophil elastase, a significant proportion remain undefined at a molecular level. A mutation (Leu270Pro) in the gene encoding the Wiskott-Aldrich syndrome protein (WASp) resulting in an X-linked SCN kindred has been reported. We therefore screened the WAS gene in 14 young SCN males with wild-type ELA2 and identified 2 with novel mutations, one who presented with myelodysplasia (Ile294Thr) and the other with classic SCN (Ser270Pro). Both patients had defects of immunologic function including a generalized reduction of lymphoid and natural killer cell numbers, reduced lymphocyte proliferation, and abrogated phagocyte activity. In vitro culture of bone marrow progenitors demonstrated a profound reduction in neutrophil production and increased levels of apoptosis, consistent with an intrinsic disturbance of normal myeloid differentiation as the cause of the neutropenia. Both mutations resulted in increased WASp activity and produced marked abnormalities of cytoskeletal structure and dynamics. Furthermore, these results also suggest a novel cause of myelodysplasia and that male children with myelodysplasia and disturbance of immunologic function should be screened for such mutations.
Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients
Authors: Caruso Vanesa , Iacoviello Licia , Di Castelnuovo Augusto , Storti Sergio , Mariani Guglielmo , de Gaetano Giovanni , Donati Maria Benedetta
Published: June 2006

The risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk.
Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplantation model
Authors: Cheretakis Chrisovalantou , Leung Roland , Sun Chun Xiang , Dror Yigal , Glogauer Michael
Published: June 2006

It has been suggested that neutrophil tissue repopulation following bone marrow transplantation (BMT) serves as an earlier and more relevant marker of susceptibility to infection than circulating neutrophil counts. In a previous study using an oral rinse protocol, we found that oral neutrophil recovery always preceded blood neutrophil engraftment and that the day of oral neutrophil detection served as a predictor of patient susceptibility to infection after BMT. Consequently, we have developed and validated a mouse BMT model which uses bone marrow transplants containing enhanced green fluorescent protein-expressing neutrophils to follow neutrophil tissue repopulation after BMT. Using this in vivo cell migration model, we assessed the significance of neutrophil tissue recruitment kinetics with neutrophil functionality and in vivo bacterial killing after BMT. Using the animal model, we have demonstrated that protection against bacterial infection is conferred at the time of neutrophil tissue delivery, which always occurs before neutrophils are detected in the blood. We therefore conclude that neutrophil tissue recovery is an early measure of the restoration of cellular innate immune function after BMT. This model will help us better understand the factors regulating neutrophil recruitment to the tissues.
Molecular events contributing to cell death in malignant human hematopoietic cells elicited by an IgG3-avidin fusion protein targeting the transferrin receptor
Authors: Ng Patrick P. , Helguera Gustavo , Daniels Tracy R. , Lomas Simon Z. , Rodriguez Jose A. , Schiller Gary , Bonavida Benjamin , Morrison Sherie L. , Penichet Manuel L.
Published: June 2006

We have previously reported that an anti-human transferrin receptor IgG3-avidin fusion protein (anti-hTfR IgG3-Av) inhibits the proliferation of an erythroleukemia-cell line. We have now found that anti-hTfR IgG3-Av also inhibits the proliferation of additional human malignant B and plasma cells. Anti-hTfR IgG3-Av induces internalization and rapid degradation of the TfR. These events can be reproduced in cells treated with anti-hTfR IgG3 cross-linked with a secondary Ab, suggesting that they result from increased TfR cross-linking. Confocal microscopy of cells treated with anti-hTfR IgG3-Av shows that the TfR is directed to an intracellular compartment expressing the lysosomal marker LAMP-1. The degradation of TfR is partially blocked by cysteine protease inhibitors. Furthermore, cells treated with anti-hTfR IgG3-Av exhibit mitochondrial depolarization and activation of caspases 9, 8, and 3. The mitochondrial damage and cell death can be prevented by iron supplementation, but cannot be fully blocked by a pan-caspase inhibitor. These results suggest that anti-hTfR IgG3-Av induces lethal iron deprivation, but the resulting cell death does not solely depend on caspase activation. This report provides insights into the mechanism of cell death induced by anti-TfR Abs such as anti-hTfR IgG3-Av, a molecule that may be useful in the treatment of B-cell malignancies such as multiple myeloma.
Regulatory T Cells in Human Autoimmune Thyroid Disease
Authors: Marazuela Mónica , García-López María A. , Figueroa-Vega Nicté , de la Fuente Hortensia , Alvarado-Sánchez Brenda , Monsiváis-Urenda Adriana , Sánchez-Madrid Francisco , González-Amaro Roberto
Published: June 2006

Context: T regulatory cells have a key role in the pathogenesis of autoimmune diseases in different animal models. However, less information is available regarding these cells in human autoimmune thyroid diseases (AITD).

Objective: The objective of the study was to analyze different regulatory T cell subsets in patients with AITD.

Design: We studied by flow cytometry and immunohistochemistry different T regulatory cell subsets in peripheral blood mononuclear cells (PBMCs) and thyroid cell infiltrates from 20 patients with AITD. In addition, the function of TREG lymphocytes was assessed by cell proliferation assays. Finally, TGF-β mRNA in thyroid tissue and its in vitro synthesis by thyroid mononuclear cells (TMCs) was determined by RNase protection assay and quantitative PCR.

Results: PBMCs from AITD patients showed an increased percent of CD4+ lymphocytes expressing glucocorticoid-induced TNF receptor (GITR), Foxp3, IL-10, TGF-β, and CD69 as well as CD69+CD25bright, CD69+TGF-β, and CD69+IL-10+ cells, compared with controls. TMCs from these patients showed an increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing CD25bright, GITR, and Foxp3, compared with autologous PBMCs. Furthermore, a prominent infiltration of thyroid tissue by CD69+, CD25+, and GITR+ cells, with moderate levels of Foxp3+ lymphocytes, was observed. The suppressive function of peripheral blood TREG cells was defective in AITD patients. Finally, increased levels of TGF-β mRNA were found in thyroid tissue, and thyroid cell infiltrates synthesized in vitro significant levels of TGF-β upon stimulation through CD69.

Conclusions: Although T regulatory cells are abundant in inflamed thyroid tissue, they are apparently unable, in most cases, to downmodulate the autoimmune response and the tissue damage seen in AITD.
Effects of Dehydroepiandrosterone and Atamestane Supplementation on Frailty in Elderly Men
Authors: Muller Majon , van den Beld Annewieke W. , van der Schouw Yvonne T. , Grobbee Diederick E. , Lamberts Steven W. J.
Published: June 2006

Background: It has been suggested that the age-related decline of androgens in men plays a distinct role in the development of several aspects of frailty. Therefore, hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength, decreasing fat mass, and improving the subjective quality of life.

Objective: The objective of the study was to assess whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane might improve the course of frailty.

Design: This was a double-blind, randomized, controlled trial.

Setting: The study was conducted in the general community.

Participants: Participants included 100 nonhospitalized, nondiseased, independently living men, aged 70 yr and over with low scores on strength tests. Seventeen participants did not complete the trial.

Intervention: Subjects were randomly assigned to one of four intervention arms: atamestane (100 mg/d) and placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and DHEA (50 mg/d), or two placebo tablets for 36 wk.

Main Outcome Measures: Physical frailty was measured by means of a specific test battery, including isometric grip strength, leg extensor power, and physical performance.

Results: The randomization was successful, and 83 (83%) men completed the intervention. There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention.

Conclusions: The results of this double-blind, randomized trial do not support the hypothesis that hormone replacement with DHEA and/or atamestane might improve the course of frailty.
Low-Dose Rosiglitazone Exerts an Antiinflammatory Effect with an Increase in Adiponectin Independently of Free Fatty Acid Fall and Insulin Sensitization in Obese Type 2 Diabetics
Authors: Ghanim Husam , Dhindsa Sandeep , Aljada Ahmad , Chaudhuri Ajay , Viswanathan Prabhakar , Dandona Paresh
Published: June 2006

Background: We have previously demonstrated an early and potent antiinflammatory effect of troglitazone and rosiglitazone.

Hypothesis: Because inflammatory mediators interfere with insulin signal transduction, we have now hypothesized that rosiglitazone exerts an initial antiinflammatory effect independently of its metabolic actions including the suppression of the plasma concentration of free fatty acids (FFAs), insulin, and glucose after which insulin sensitization occurs.

Patient and Methods: Fourteen patients with type 2 diabetes were included in the study. Eight patients were given 2 mg daily of rosiglitazone for 6 wk, whereas the other six patients were given a placebo for the same period.

Results: After a 2-mg dose of rosiglitazone, plasma FFAs, insulin, and glucose concentrations and homeostasis model assessment of insulin resistance did not change. Plasma C-reactive protein, serum amyloid A, and matrix metalloproteinase concentrations fell significantly at wk 1 and continued to be significantly lower than the baseline levels by 25, 29, and 24%, respectively, at wk 6. Leukocyte count was significantly lower at wk 6 after rosiglitazone, whereas there was no change in the control group. Plasma adiponectin concentrations increased significantly at wk 2 and continued to increase during the treatment period with rosiglitazone. Resistin concentrations fell significantly by 10% at wk 6 only. There were no changes in any of these indices in the placebo group.

Conclusions: A low dose of rosiglitazone exerts an early and potent antiinflammatory effect with an increase in adiponectin and a fall in resistin concentrations without causing any metabolic changes (fall in plasma glucose, FFAs, and insulin concentrations) over a 6-wk period. The increase in adiponectin and the decrease in resistin after rosiglitazone are thus related primarily to its antiinflammatory effects rather than its metabolic actions. These observations have implications in relation to the mode of action of this drug as an insulin-sensitizing agent and also its use as a potential antiinflammatory and antiatherogenic drug in the future.
The A645D Mutation in the Hinge Region of the Human Androgen Receptor (AR) Gene Modulates AR Activity, Depending on the Context of the Polymorphic Glutamine and Glycine Repeats
Authors: Werner Ralf , Holterhus Paul-Martin , Binder Gerhard , Schwarz Hans-Peter , Morlot Michel , Struve Dagmar , Marschke Christine , Hiort Olaf
Published: June 2006

Background: Sufficient androgen receptor (AR) activity is crucial for normal male sexual differentiation. Here we report on two unrelated 46, XY patients suffering from undervirilization and genital malformations. Both patients had a short polyglycine (polyG) repeat of 10 residues and a relatively long polyglutamine (polyQ) repeat of 28 and 30 residues within the transactivation domain of the AR. In addition, they also harbor a rare A645D substitution.

Objective: We made a set of AR expression plasmid constructs with varying polyQ and polyG tract sizes in context with or without the A645D substitution and analyzed their in vitro transactivation capacity in transfected CHO cells.

Results: We found that a short polyG repeat downmodulated AR activity to approximately 60–65% of the wild-type receptor. This effect was aggravated by A645D in context of a long polyQ repeat to less than 50% activity. In contrast, in the context of a short polyQ and a short polyG repeat, the A645D mutation rescues AR activity to almost wild-type levels, demonstrating a contradictory effect of this mutation, depending on the size of the polymorphic repeats.

Conclusions: A combination of a short polyG repeat with a long polyQ repeat and an A645D substitution might contribute to the development of virilization disorders and explain the observed phenotypes of our patients as a form of androgen insensitivity. The whole recreation of AR sequence variations including individual polymorphic repeat sizes could unravel possible interference of mutations and variations on AR activity by in vitro transfection.
Mosaicism of a Thyroid Hormone Receptor-β Gene Mutation in Resistance to Thyroid Hormone
Authors: Mamanasiri Sunee , Yesil Sena , Dumitrescu Alexandra M. , Liao Xiao-Hui , Demir Tevfik , Weiss Roy E. , Refetoff Samuel
Published: June 2006

Context: Heterozygous mutations in thyroid hormone receptor-β (TRβ) gene are the cause of resistance to thyroid hormone (RTH) in more than 85% of families having the syndrome. In 23% of the families, TRβ gene mutations occur de novo. Of the 141 families with RTH investigated by us, 21 (15%) had no TRβ gene mutations detectable by sequencing from genomic DNA (gDNA) or cDNA (non-TR RTH).

Objective: The objective of the study was to investigate the genotype of a family with RTH and correlate it to the phenotype.

Design: The DNA was isolated from different tissues, and the sequence of the TRβ gene was determined. Clinical studies involved the administration of incremental doses of T3.

Setting: The study was conducted at a referral pediatric endocrinology clinic in Turkey and an academic medical center in the United States.

Main Outcome and Measures: Measurement included markers of thyroid hormone action and sequencing of TRβ revealing a R338W mutation.

Patients and Family: We studied two siblings with short stature, panic disorder, psychosis, and high free iodothyronine concentrations with nonsuppressed TSH and their father with similar thyroid function tests without growth or psychiatric abnormalities.

Results: Direct sequencing of gDNA obtained from the father’s leukocytes, buccal mucosa cells, and prostate tissue showed less amplification of the mutant allele (R338W) than the normal allele as confirmed by PCR/restriction fragment length polymorphism analysis. No sequence abnormalities were detected in gDNA from fibroblasts. Similar results were found in mRNA from the leukocytes and fibroblasts. The sensitivity of various tissues to thyroid hormone was not uniform. The progeny had equal amounts of mutant and wild-type gDNA in leukocytes and skin.

Conclusions: The father has a mosaicism for the R338W mutation as it was present in some cell lineages, including his germline, because it was transferred to his children but not in fibroblasts. This indicates that the mutation occurred de novo in early embryonic life. Here is the first report of mosaicism in RTH. The possibility of mosaicism should be considered in subjects with RTH without apparent mutations in the TRβ gene.
Thyroid Function Is Intrinsically Linked to Insulin Sensitivity and Endothelium-Dependent Vasodilation in Healthy Euthyroid Subjects
Authors: Fernández-Real Jose-Manuel , López-Bermejo Abel , Castro Antoni , Casamitjana Roser , Ricart Wifredo
Published: June 2006

Context: Levels of TSH respond to fluctuations in serum free T4 (fT4) but remain in a very narrow individual range. There exists current controversy regarding the upper limit of normal serum TSH values above which treatment should be indicated.

Objective: We aimed to study whether the individually determined fT4-TSH relationship was associated with plasma lipids, insulin sensitivity, and endothelial dysfunction in healthy subjects with strictly normal thyroid function according to recent recommendations (0.3–3.0 mU/liter).

Design: This was a cross-sectional study.

Setting: The study consisted of a cohort of healthy men from the general population (n = 221).

Main Outcome Measures: Oral glucose tolerance, insulin sensitivity (SI, minimal model), endothelium-dependent vasodilation (high-resolution ultrasound), and plasma lipids were measured in relation to thyroid function tests.

Results: Both serum TSH and fT4·TSH product were positively associated with fasting and postload insulin concentration and negatively with SI. After body mass index stratification, these associations were especially significant among lean subjects. Serum TSH and fT4·TSH product also correlated positively with fasting triglycerides and negatively with high-density lipoprotein cholesterol. In a multiple linear regression analysis, age (P = 0.007) and SI (P = 0.02) but not body mass index, fasting triglycerides, or serum high-density lipoprotein concentration contributed independently to 3.7 and 3.3%, respectively, of the variance in fT4·TSH. Those subjects over the median of fT4·TSH showed reduced endothelium-dependent vasodilation.

Conclusions: Thyroid function tests are intrinsically linked to variables of insulin resistance and endothelial function. It is possible that underlying factors lead simultaneously to increased serum TSH, insulin resistance, ensuing dyslipidemia, and altered endothelial function even within current normal TSH levels.
Redox regulation of CD21 shedding involves signaling via PKC and indicates the formation of a juxtamembrane stalk
Authors: Aichem Annette , Masilamani Madhan , Illges Harald
Published: June 2006

Soluble CD21 (sCD21), released from the plasma membrane by proteolytic cleavage (shedding) of its extracellular domain (ectodomain) blocks B cell/follicular dendritic cell interaction and activates monocytes. We show here that both serine- and metalloproteases are involved in CD21 shedding. Using the oxidant pervanadate to mimic B cell receptor activation and thiol antioxidants such as N-acetylcysteine (NAC) and glutathione (GSH) we show that CD21 shedding is a redox-regulated process inducible by oxidation presumably through activation of a tyrosine kinase-mediated signal pathway involving protein kinase C (PKC), and by reducing agents that either directly activate the metalloprotease and/or modify intramolecular disulfide bridges within CD21 and thereby facilitate access to the cleavage site. Lack of short consensus repeat 16 (SCR16) abolishes CD21 shedding, and opening of the disulfide bridge between cys-2 (Cys941) and cys-4 (Cys968) of SCR16 is a prerequisite for CD21 shedding. Replacing these cysteines with selenocysteines (thereby changing the redox potential from –180 to –381 mV) results in a loss of inducible CD21 shedding, and removing this bridge by exchanging these cysteines with methionines increases CD21 shedding.
Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression ofKcnq4and prestin during final differentiation of outer hair cells
Authors: Winter Harald , Braig Claudia , Zimmermann Ulrike , Geisler Hyun-Soon , Fränzer Jürgen-Theodor , Weber Thomas , Ley Matthias , Engel Jutta , Knirsch Martina , Bauer Karl , Christ Stephanie , Walsh Edward J. , McGee JoAnn , Köpschall Iris , Rohbock Karin , Knipper Marlies
Published: June 2006

Thyroid hormone (TH or T3) and TH-receptor β (TRβ) have been reported to be relevant for cochlear development and hearing function. Mutations in the TRβ gene result in deafness associated with resistance to TH syndrome. The effect of TRα1 on neither hearing function nor cochlear T3 target genes has been described to date. It is also uncertain whether TRα1 and TRβ can act simultaneously on different target genes within a single cell. We focused on two concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the expression of the prestin gene through TRβ. Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRα1 aporeceptors mediated by an identified THresponse element, which modulates KCNQ4 promoter activity. We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRα1 in final cell differentiation.
NFAT3 is specifically required for TNF-α-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells
Authors: Yan Yan , Li Jingxia , Ouyang Weiming , Ma Qian , Hu Yu , Zhang Dongyun , Ding Jin , Qu Qingshan , Subbaramaiah Kotha , Huang Chuanshu
Published: June 2006

NFAT family is recognized as a transcription factor for inflammation regulation by inducing the expression of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), the key mediator of inflammation, which was reported to induce cell transformation in mouse epidermal Cl41 cells. In this study, we demonstrated that TNF-α was able to induce NFAT activation, as well as the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The induction of COX-2 by TNF-α was abolished by knockdown of NFAT3 with its siRNA, while the induction of iNOS was not effected. Moreover, TNF-α-induced anchorage-independent cell growth was significantly inhibited by NFAT3 siRNA and cyclosporine A, a chemical inhibitor for the calcineurin/NFAT pathway, which suggests the importance of NFAT3 in regulating TNF-α-induced anchorage-independent cell growth. Consequently, impairment of COX-2 by its siRNA or selective inhibitor also inhibited TNF-α-induced anchorage-independent cell growth. Taken together, our results indicate that NFAT3 plays an important role in the regulation of TNF-α-induced anchorage-independent cell growth, at least partially, by inducing COX-2 expression in Cl41 cells. These findings suggest that NFAT3/cyclooxygenase-2 act as a link between inflammation and carcinogenesis by being involved in the tumor promotion stage.
Initiation of cofilin activity in response to EGF is uncoupled from cofilin phosphorylation and dephosphorylation in carcinoma cells
Authors: Song Xiaoyan , Chen Xiaoming , Yamaguchi Hideki , Mouneimne Ghassan , Condeelis John S. , Eddy Robert J.
Published: June 2006

It has been demonstrated that the actin-severing activity of cofilin can be downregulated by LIM kinase (LIMK)-dependent phosphorylation at residue Ser3. Chemotactic stimulaton in various cell types induces cofilin dephosphorylation, suggesting that cofilin activation in these cells occurs by a dephosphorylation mechanism. However, resting metastatic carcinoma cells have the majority of their cofilin in a dephosphorylated but largely inactive state. Stimulation with epidermal growth factor (EGF) induces an increase in cofilin activity after 60 seconds together with an increase in phosphorylated cofilin (p-cofilin), indicating that cofilin dephosphorylation is not coupled to cofilin activation in these cells. Suppression of LIMK function by inhibiting Rho-associated protein kinase (ROCK) or LIMK siRNA inhibited the EGF-induced cofilin phosphorylation but had no effect on cofilin activity or cofilin-dependent lamellipod protrusion induced by EGF. Correlation analysis revealed that cofilin, p-cofilin and LIMK are not colocalized, and changes in the location of these proteins upon stimulation with EGF indicate that they are not functionally coupled. Phospholipase C, which has been implicated in cofilin activation following stimulation with EGF, does not regulate p-cofilin levels following stimulation with EGF. Therefore, our results do not support a model for the initial activation of cofilin by dephosphorylation in response to chemoattractant stimulation in metastatic carcinoma cells.
Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells
Authors: Grati M'hamed , Aggarwal Nisha , Strehler Emanuel E. , Wenthold Robert J.
Published: June 2006

The plasma membrane Ca2+-ATPase-2 (PMCA2) is expressed in stereocilia of hair cells of the inner ear, whereas PMCA1 is expressed in the basolateral plasma membrane of hair cells. Both extrude excess Ca2+ from the cytosol. They are predicted to contain ten membrane-spanning segments, two large cytoplasmic loops as well as cytosolic N- and C-termini. Several isoform variants are generated for both PMCA1 and PMCA2 by alternative splicing, affecting their first cytosolic loop (A-site) and their C-terminal tail. To understand how these isoforms are differentially targeted in hair cells, we investigated their targeting regions and expression in hair cells. Our results show that a Leu-Ile motif in `b'-tail splice variants promotes PMCA1b and PMCA2b basolateral sorting in hair cells. Moreover, apical targeting of PMCA2 depends on the size of the A-site-spliced insert, suggesting that the conformation of the cytoplasmic loop plays a role in apical targeting.
Influence of human Ect2 depletion and overexpression on cleavage furrow formation and abscission
Authors: Chalamalasetty Ravindra B. , Hümmer Stefan , Nigg Erich A. , Silljé Herman H. W.
Published: June 2006

The guanine nucleotide-exchange factor (GEF) Ect2 is essential for cytokinesis. Here we studied the subcellular localization of Ect2 and examined the consequences of either depleting or overexpressing Ect2 in human cells. We show that in mitotic cells Ect2 localizes to the central spindle and to the cell cortex. The latter association is mediated through a PH domain in Ect2 and central spindle localization requires the MKlp1-MgcRacGAP and MKlp2–Aurora-B complexes. Ect2 directly interacts with MKlp1-MgcRacGAP through its BRCT domain, whereas MKlp2–Aurora-B probably exerts a regulatory role in Ect2 central spindle targeting. Depletion of Ect2 impaired cleavage furrow formation and RhoA and Citron kinase failed to accumulate at the cleavage furrow. Ect2 displacement from the central spindle revealed that physiological levels of this protein in this location are not crucial for RhoA activation and cytokinesis. In cells overexpressing appropriate N-terminal Ect2 fragments, RhoA and Citron kinase localized to the cleavage furrow and ingression occurred, but abscission failed. This failure could be correlated with the persistence of these fragments at structures surrounding the midbody, suggesting that abscission requires the displacement of Ect2 from the contractile ring and its re-import into the nucleus.
Development of Electron-Ion Coincidence Spectroscopy for the Study of Surface Dynamics
Authors: Mase Kazuhiko , Nagasono Mitsuru , Urisu Tsuneo , Murata Yoshitada
Published: June 2006

Electron-ion coincidence (EICO) spectroscopy for studying surface dynamics has been developed. The apparatus consists of an electron gun, a cylindrical mirror analyzer (CMA), and a time-of-flight ion mass spectrometer (TOF-MS). A sample surface is excited with an electron beam, and the energy of the emitted electrons is analyzed by the CMA. The TOF spectra of desorbed ions are measured with the TOF-MS and a multichannel scaler, taking the energy-analyzed electron signal as the starting trigger. Those ions coincidently desorbed with electrons give a characteristic peak in the TOF spectrum. The apparatus has been evaluated on the basis of electron-ion coincidence measurements of an F/SrTiO3 (100) surface. The F+ coincidence signal was observed to be enhanced at electron kinetic energies of 650—655 eV, corresponding to the F(KL23L23) Auger transition. The result provides direct evidence of the Auger-stimulated ion-desorption mechanism for an ionically bonded surface (the Knotek–Feibelman (KF) mechanism).
Proposed Mechanism of Ferromagnetic Interaction of Organic Ferromagnets: 4-(Arylmethyleneamino)-2,2,6,6-tetramethylpiperidin-1-oxyls and Related Compounds
Authors: Nogami Takashi , Ishida Takayuki , Yasui Masanori , Iwasaki Fujiko , Takeda Naoya , Ishikawa Masayasu , Kawakami Takashi , Yamaguchi Kizashi
Published: June 2006

A possible mechanism of ferromagnetic coupling of a series of organic radical ferromagnets is presented, based on their crystal structures and molecular-orbital calculations. The investigated radicals are 4-(arylmethyleneamino)-2,2,6,6-tetramethylpiperidin-1-oxyls (abbreviated as Ar–CH=N–TEMPO, where Ar = phenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-biphenylyl, and 4-phenoxyphenyl), and 4-hydroxyimino-TEMPO. All of these radical crystals have characteristic features that oxygen atoms of N–O radical sites of TEMPO moieties always locate near methyl- and/or methylene-hydrogens at β-positions of N–O in the TEMPO moieties of adjacent molecules. A positive spin on the N–O radical induces negative spins on the β-hydrogen atoms due to an intramolecular spin-polarization, ON(↑)–C(↓)–C(↑)–H(↓), which in turn induces a positive spin on the N–O sites of the adjacent molecules. This spin-alternation mechanism of ferromagnetic coupling among N–O sites via hydrogen bridges is also applicable to the case of an organic metamagnet, bis(2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl) 1,6-hexanedicarboxylate. In the case of an organic ferromagnet, 2,4,6,8-tetramethyl-1,5-diazaadamantane-1,5-dioxyl, both the spin-alternation and direct exchange mechanisms seem to be operative.
Structure and Properties of Titanium-Including Complex, Tris(tetramethyltetrathiafulvalene) Di-μ-fluoro-bis[tetrafluorotitanate(IV)], (TMTTF)3Ti2F10
Authors: Akutsu Hiroki , Ozeki Katsunari , Ozaki Takayuki , Nozawa Kiyokazu , Kinoshita Minoru , Kozawa Kozo , Uchida Tokiko
Published: June 2006

A novel molecular complex of tetramethyltetrathiafulvalene (TMTTF) was prepared by the treatment with TiF4. The X-ray analysis reveals the exsistence of a trimer of TMTTF’s and a Ti2F102− anion in a triclinic unit cell of the dimension; a = 10.934(3), b = 12.798(2), c = 8.000(1) Å, α = 103.86(1), β = 107.08(2), γ = 75.02(2)°. All the molecular planes of TMTTF are nearly parallel. The trimers stack parallel to the a axis, and the intertrimer interaction is estimated to be weak. A semiconductive behavior with a relatively large Seebeck coefficient was observed (ρ = 3 × 102 Ω cm, Ea = 0.26 eV, and S = −0.41 mV K−1 along the a axis). Weak electron spin resonance (ESR) absorption was observed to be characteristic of low-dimensional diffusive spin systems.
Order Parameter and Density Effects in the Third-Order Nonlinear Optical Properties of Liquid Crystals
Authors: Terazima Masahide
Published: June 2006

Third-order nonlinear optical effects induced by thermal and photochemical reactions after a real photoexcitation of neat (undoped) liquid crystals (N-(4-methoxybenzylidene)-4-butylaniline (MBBA) and cyanopentylbiphenyl) were investigated by the transient grating method with nanosecond and picosecond pulsed-laser systems. The origins of the effect were clearly separated into the density and order parameter changes by a polarization selection of the probe beam; also, the dynamics (speed of the changes) of both components were investigated. The decrease in the density under the presence of the cis form of MBBA was observed and could be explained in terms of a void volume effect.
Suppression of Growth Instability in Electropolymerization of Pyrrole
Authors: Mogi Iwao , Kamiko Masao
Published: June 2006

The pattern formation of electropolymerized polypyrrole was studied in bulk-solution and thin-layer-solution cells with and without a magnetic field. A diffusion-limited aggregation pattern was observed in the bulk-solution cell in the absence of a magnetic field. The growth instability was found to be suppressed by thinning the solution and the application of the magnetic field.