bluuebunny/crossref_metadata_2025 huggingface dataset:
Visfatin expression is hormonally regulated by metabolic and sex hormones in 3T3‐L1 pre‐adipocytes and adipocytes
Authors: MacLaren R. , Cui W. , Cianflone K.
Published: August 2006

Aim:  The novel adipokine visfatin has ‘insulin‐mimicking’ effects and is increased in models of diet‐induced obesity, but factors that regulate visfatin have not been fully elucidated.

Methods:  In order to determine visfatin regulation in adipocyte development and metabolism, as well as in pathophysiological conditions related to metabolic syndrome, endogenous visfatin expression was measured in 3T3‐L1 pre‐adipocytes and adipocytes using real‐time reverse transcriptase polymerase chain reaction (real‐time RT‐PCR).

Results:  A marked increase in visfatin expression was observed during differentiation, with a 2.2‐fold increase between preconfluent and 2‐day confluent cells even before differentiation was initiated. A further 4.1‐fold increase was induced from day 0 to day 9 of differentiation (overall ninefold). Overnight incubation with dexamethasone (10−8 to 10−2 M) increased visfatin expression in both pre‐adipocytes (1.5‐ to 3.3‐fold, p < 0.05) and adipocytes (1.9‐fold, p < 0.01). All other treatments decreased visfatin expression. In pre‐adipocytes, visfatin expression decreased by 23% at a concentration of 1 μM insulin, 15% at 1–15 nM T3, 15% at 10 nM–1 μM progesterone, 33–44% at 10 nM–1 μM testosterone, 50% with palmitate and 30% with oleate (p < 0.05 for all). In adipocytes, insulin had a much greater effect, decreasing visfatin by 77% at 100 nM (p < 0.01), whereas oleate and sex hormones did not affect visfatin expression. However, tumor necrosis factor α, which had no effect on pre‐adipocytes, significantly decreased visfatin in adipocytes by 26% at 10 ng/ml (p < 0.05). Interestingly, the thiazolidinedione (TZD) rosiglitizone also decreased visfatin by 28% at a concentration of 1 μM (p < 0.01).

Conclusion:  In summary, while the mechanism of visfatin action remains to be elucidated, the clear effects of multiple hormones on visfatin expression support a physiological role.
Isosteviol reduces plasma glucose levels in the intravenous glucose tolerance test in Zucker diabetic fatty rats
Authors: Ma J. , Ma Z. , Wang J. , Milne R. W. , Xu D. , Davey A. K. , Evans A. M.
Published: August 2006

Aim:  The aim of this study was to test the effect of isosteviol on blood glucose and insulin levels during the intravenous glucose tolerance test (IVGTT) in Wistar and Zucker diabetic fatty (ZDF) rats.

Methods:  ZDF rats were divided into a control and three isosteviol treatment (1, 5 and 10 mg/kg) groups. Wistar rats were divided into a control group and an isosteviol treatment group (10 mg/kg). The rats were fasted for 12 h prior to infusion of isosteviol and glucose (1.0 g/kg). Blood samples were taken at 0, 5, 15, 30, 60, 90 and 120 min after the injection of glucose. Glucose concentrations were determined by the glucose oxidase method, and plasma insulin was analysed by radioimmunoassay. The area under the curve (AUC) of the net change in plasma glucose concentration was used to compare the isosteviol treatment and control groups.

Results:  In ZDF rats, isosteviol at 5 and 10 mg/kg caused a significant (p < 0.05) reduction in the AUC of glucose during the IVGTT. However, isosteviol did not increase plasma insulin concentrations in ZDF rats. In Wistar rats, isosteviol did not significantly affect plasma glucose or insulin levels during the IVGTT.

Conclusion:  Isosteviol exerts an antihyperglycaemic effect during IVGTT in ZDF rats but not in Wistar rats. Isosteviol has no significant effect on plasma insulin concentrations. The glucose‐lowering effect of isosteviol may be due to changes in the sensitivity of peripheral tissues to insulin.
Effect of pioglitazone in combination with insulin therapy on glycaemic control, insulin dose requirement and lipid profile in patients with type 2 diabetes previously poorly controlled with combination therapy
Authors: Berhanu P. , Perez A. , Yu S.
Published: August 2006

Aim:  The aim of this randomized placebo‐controlled study was to evaluate the safety and efficacy of pioglitazone administered alone or in combination with metformin in reducing insulin dosage requirements for improved glycaemic control in patients with type 2 diabetes previously poorly controlled with combination therapy.

Methods:  In this multicentre, double‐blind study, 222 patients with haemoglobin A1c (HbA1c)>8.0% at screening treated with combination therapy initially were given titrated insulin therapy (to fasting plasma glucose <140 mg/dl) and then were randomly assigned to 20‐week treatment with pioglitazone or placebo in combination with insulin, with or without concurrent metformin therapy. More than 98% of patients were taking metformin prior to and during the study.

Results:  Pioglitazone significantly reduced (p < 0.05) insulin dose requirements 2 weeks after treatment initiation. At study end relative to baseline, pioglitazone reduced daily insulin dosages by 12.0 units (p < 0.001), a 21.5% (12.0/55.8 units at baseline) group mean average reduction. Relative to placebo, pioglitazone reduced daily insulin dosages by 12.7 units [95% confidence interval [CI]: −17.5, −8.0], while improving mean HbA1c levels [adjusted mean HbA1c change: pioglitazone, −1.6% vs. placebo, −1.4% (not statistically different)]. Pioglitazone also significantly increased high‐density lipoprotein cholesterol levels [adjusted mean difference: +4.5 (95% CI: 2.6–6.5) mg/dl], decreased triglyceride levels [−43.9 (−69.2, −18.6) mg/dl], shifted low‐density lipoprotein (LDL) particle concentrations from small [pattern B, −13.6% (−17.7%, −9.5%)] to large [pattern A, +15.1% (10.8%, 19.5%)] and increased mean LDL particle size [+3.8 (2.6, 4.9) Å]. More pioglitazone‐treated patients experienced oedema (9.0 vs. 4.5%) and weight gain (9.1 vs. 2.7%) than placebo patients.

Conclusions:  Pioglitazone in combination with insulin therapy improved glycaemic control, reduced insulin dose requirements and improved lipid profiles in patients with type 2 diabetes previously poorly controlled with combination therapy.
Why Some Firms Train Apprentices and Many Others Do Not
Authors: Wolter Stefan C. , Schweri Jürg , Mühlemann Samuel
Published: August 2006

The latest study investigating the cost-benefit ratio of apprenticeship training for Swiss companies has shown that most apprentices offset the cost of their training during their apprenticeship on the basis of the productive contribution of the work they perform. Given this outcome, it is worth investigating why so many firms choose not to train apprentices. Maximum-likelihood selection models were used to estimate the net cost of training for firms without an apprenticeship programme. The models show, firstly, that non-training firms would incur significantly higher net cost during the apprenticeship period if they would switch to a training policy and, secondly, that this less favourable cost-benefit ratio is determined less by cost than by absence of benefit. For the apprenticeship system as such the results indicate that, as long as training regulations and the market situation permit a cost-effective training of apprentices, companies do not need specific labour market regulations or institutions to offer training posts. In this respect, the Swiss findings might be of interest for the ongoing German discussion about the expected repercussions of a more general labour market deregulation on the apprenticeship training system.
Skill Loss, Ranking of Job Applicants and the Dynamics of Unemployment
Authors: Eriksson Stefan
Published: August 2006

This paper investigates the consequences of skill loss as a result of unemployment in an efficiency wage model with turnover costs and on-the-job search. Firms are unable to differentiate wages and therefore prefer to hire employed searchers or unemployed workers who have not lost human capital. It is shown that if some fundamental factor in the economy changes, this will result in a lengthy adjustment process with substantial long-run unemployment effects. Moreover, the model is capable of generating persistence, but the amount depends on the duration of the shock itself.
Effectiveness versus Efficiency: Growth-Accelerating Policies in a Model of Growth without Scale Effects
Authors: Büttner Bettina
Published: August 2006

Recent R&D growth models without strong scale effects imply that long-run growth rates depend only on parameters that are usually taken to be exogenous. However, integrating human capital accumulation into models of this type, Arnold (2002) demonstrates that subsidizing education accelerates growth. The present paper addresses welfare issues in Arnold’s model. The main theoretical finding of the paper is that a system of subsidies that implements the optimal balanced growth path as a decentralized equilibrium includes zero subsidies to education, while R&D activity should be either subsidized or taxed. To shed further light on the latter result, the model is calibrated and it turns out that along the balanced growth path, the decentralized economy underinvests in R&D, i.e. R&D activities should be subsidized.
Basal cell carcinoma arising over facial port wine stain: a single‐centre experience
Authors: Lapidoth M , Ad‐El D , David M , Alcalay J , Azaria R
Published: August 2006

Background  A growing number of reports point to a possible connection between basal cell carcinoma (BCC) and port wine stain (PWS). Researchers suggest that either the elevated temperature induced by the increased dermal vasculature or an oncogenic factor produced by the ectatic vessels makes the overlying epidermis more susceptible to ultraviolet or ionizing radiation.

Objective  To check the prevalence of BCC in patients with PWS at a large national vascular amomalies centre.

Methods  The study group included 68 patients, 44 women and 24 men, with facial PWSs. Detailed data were collected on background features, past treatments and past exposure to radiation, and a comprehensive physical examination was performed. Biopsy samples were taken from suspect lesions for histological study.

Results  Four patients (5.9%) were found to have histologically proven BCC, 3 nodular and one multifocal. All had been exposed to radiation during childhood. Treatment consisted of excision; there was one recurrence.

Conclusion  Although the co‐occurrence of BCC and PWS is probably related to radiation treatment in childhood, these findings should alert physicians to regularly examine PWSs for cancerous changes, especially in patients at risk.
Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection
Authors: Lecha M , Badenas C , Puig S , Orfila J , Milà M , To‐Figueras J , Muñoz C , Mercader P , Herrero C
Published: August 2006

Objectives  First, to establish the mutations of the protoporphyrinogen‐oxidase (PPOX) gene in four Spanish patients with variegate porphyria (VP). Second, study of carrier status detection in the families, including a four‐generation Balearic family. Third, evaluation of the results of carrier detection screening methods.

Design  Blood samples of four patients and of 139 members belonging to four families, including four generations of a Balearic family were processed for mutation analysis of the 13 exons of PPOX gene. Biochemical studies were performed together (blood and faecal porphyrin analysis) and plasma fluorescence scanning for 626 nm peak emission detection. A questionnaire regarding clinical manifestations was submitted to all family members studied.

Results  Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077–1082insC: exon 10, and IVS6+2T→A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checked in the carriers detected and found as not relevant or not present. Only 11 members of the 19 mutation‐bearing individuals showed plasma fluorescence PV peak positivity.

Conclusion  Demonstration of gene mutation is the most reliable means of detecting carriers in studies of variegate porphyria families. DNA analysis is the most sensitive carrier detection method and also allows transmission behaviour of the genetic defect to be established in successive generations of the affected families.
Elastin changes during chronological and photo‐ageing: the important role of lysozyme
Authors: Seite S , Zucchi H , Septier D , Igondjo‐Tchen S , Senni K , Godeau G
Published: August 2006

Background  Cutaneous ageing, as a result of combined chronological and photo‐ageing in sun‐exposed areas, is accompanied by major modifications of the elastic fibres.

Aim  We aimed to investigate qualitative and quantitative changes of dermal elastin fibres during cutaneous chronological and photo‐ageing and the involvement of lysozyme in these processes.

Methods  Morphological, age‐related changes and variations in the relative elastin content in sun‐protected (buttock) and sun‐exposed (forearm and face) skin of healthy volunteers were studied (145 samples). The deposition of lysozyme in elastin fibres was studied using light and immuno‐electron microscopy and taking into consideration the relative efficacy of different UV wavebands (UVA or SSR (solar simulated radiation)). Our studies also included the proteolytic degradation of elastin by human leucocyte elastase (HLE) in situ.

Results  Our results indicate a reduction of elastin content with age in sun‐protected and sun‐exposed skin, associated for the latter with high elastin content, resulting in elastosis. Total UVA (320–400 nm), and in particular long wave UVA (UVA‐1, 340–400 nm), induces lysozyme deposition in elastin fibres to a higher extent than solar simulated radiation (SSR, 280–400 nm). Immuno‐electron microscopy revealed lysozyme association with the electron‐dense granular amorphous elastin structures, corresponding to a basophilic degeneration induced by sun exposure. Lysozyme has no elastolytic activity in situ; however, its binding to elastin limits elastin degradation by human leucocyte elastase (HLE). In addition, a direct inhibitory effect of lysozyme on HLE was observed.

Conclusion  Our data suggest that lysozyme prevents elastin degradation by HLE after binding to the damaged parts of the elastin network and by direct lysozyme–HLE interaction, which reduces HLE proteolytic activity. These observations contribute to a better understanding of the chronological and photo‐induced changes of the dermal elastic network.
Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus
Authors: Boehncke W‐H , Brasie RA , Barker J , Chimenti S , Daudén E , De Rie M , Dubertret L , Giannetti A , Katsambas A , Kragballe K , Naeyaert JM , Ortonne J‐P , Peyrí J , Prinz JC , Saurat J‐H , Strohal R , Van De Kerkhof P , Sterry W
Published: August 2006

Background  Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well‐being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label.

Objective  To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license.

Methods  An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed.

Results  It was recommended that, where possible, patients are initiated on the 50 mg twice‐weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out.

Conclusions  The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.
Monitoring Trends in Poverty and Income Distribution: Data, Methodology and Measurement
Authors: SAUNDERS PETER , BRADBURY BRUCE
Published: August 2006

Australian research on poverty and income distribution has been subject to criticism over definitional, data quality and measurement issues that have undermined its validity and impact. In reviewing these issues, this paper addresses some of the problems that have been identified in the literature and illustrates their importance with examples that shed light on the validity of the arguments. It also seeks to establish whether poverty has increased or decreased in the decade to 2002–03 and examines the overlap between hardship or deprivation and income poverty, and reviews some of the emerging evidence on the dynamics of low income. After a detailed review of data problems, the significance of definitional issues is illustrated in relation to the measurement of income inequality and poverty. Attention then focuses on assessing the sensitivity of estimated trends in income poverty to how poverty is defined and measured. Although there is variation across the different measures, the evidence suggests that progress in reducing relative poverty has been slow. Our preferred measure (based on current income) suggests that relative poverty increased slightly over the decade, with most of the increase occurring between 1995–96 and 1999–2000. When poverty is measured in ‘absolute’ terms using a poverty line that is held constant in real terms, the poverty rate declined overall, but was more or less constant between 1996–97 and 2000–01. Estimates derived from wave III of Household Income and Labour Dynamics in Australia (HILDA) data indicate that those who were income poor in 2002–03 experienced twice as many hardship conditions as those who were not poor, with around one‐quarter of the poor having problems paying bills or seeking external financial assistance. HILDA data also indicate that many of those who are in poverty in any single year manage to escape within the next 2 years, although it is too early to know whether they escape permanently, or slip back into poverty or oscillate on its margins.
Looking Back as We Look Ahead: Integrating Research, Theory, and Practice on Intergroup Relations
Authors: Nagda Biren (Ratnesh) A. , Tropp Linda R. , Paluck Elizabeth Levy
Published: August 2006

This article looks back at the origins of intergroup relations in social psychology just over 50 years ago. Pioneers in the field—Robin Williams, Gordon Allport, and Kurt Lewin—were all deeply concerned with integrating social science and social action. We seek to re‐center this mutuality of research and practice, and to expand the focus of intergroup relations from prejudice reduction to social inclusion. The articles in this issue document cutting‐edge research, theory, and practice, and make substantive contributions to the future of intergroup relations. A unique feature of this issue is a set of commentaries by prominent scholars and practitioners in the fields of intergroup relations and education. Walter Stephan, James Banks, Thomas Pettigrew, and Patricia Gurin each reflect on the collection of articles through the lens of their own personal and professional biographies to help define the intersections of research, theory, and practice on intergroup relations.
Breaking Barriers, Crossing Borders, Building Bridges: Communication Processes in Intergroup Dialogues
Authors: Nagda Biren (Ratnesh) A.
Published: August 2006

Research in intergroup contact and intergroup education is increasingly focused on the psychological and pedagogical processes to explain the impact of interventions on desired outcomes. This emerging scholarship has enriched our understanding about what types of interventions are effective or not and how these interventions impact outcomes of prejudice reduction and social inclusion. In the present study, a new theoretical dimension of processes operating in intergroup contact and education is investigated: communication processes. Factor analyses of communication processes within an intergroup encounter, using data from a pretest/posttest design with a diverse group of students (n= 211), revealed four factors: (1) appreciating difference, (2) engaging self, (3) critical self‐reflection, and (4) alliance building. Furthermore, path analysis shows that these communication processes fully mediate the impact of intergroup dialogue on bridging differences. The communication processes illuminate a deeper understanding of what happens within the context of intergroup encounters and provide a link between pedagogical strategies and psychological processes.
Bridging the Researcher‐Practitioner Divide in Intergroup Relations
Authors: Stephan Walter G.
Published: August 2006

Editors' introduction: Walter Stephan's interest in intergroup relations grew from his early involvement in intercultural relations. He spent substantial time in Latin America as well as Vietnam during his college years. These experiences influenced his choice to study social psychology at the University of Minnesota. His first foray into intergroup relations came with his move to Austin, Texas, in 1971. A Court mandate ordered schools to be desegregated, and Stephan examined the effects of school desegregation there on students' self‐esteem and intergroup attitudes. His field research on the effects of desegregation as well as classroom interventions to improve intergroup relations was complemented by his laboratory research on intergroup biases, intergroup threat, intergroup anxiety, and empathy. Stephan brings this lifetime of involvement in both basic and applied research, and deep concern for effective practice and humanistic philosophy, to his commentary. He opens the commentaries with an elucidation of the difficulties in, and benefits of, the central thrust of this volume: the researcher‐practitioner collaboration. He paints portraits of practitioners, researchers, and practitioner‐researchers, and classifies articles in this issue accordingly. He notes the difficulties among the various parties interested in improving intergroup relations, spanning from simple lack of knowledge to lack of contact to lack of meaningful ways to interact. However, potential benefits of collaboration are abundant for all parties, and Stephan proposes a number of ways in which such partnerships could be actualized.
CXOU J121538.2+361921 in the galaxy NGC 4214: a double neutron star in the making?
Authors: Dewi J. D. M.
Published: August 2006

CXOU J121538.2+361921 is the brightest X-ray source in the galaxy NGC 4214, with an X-ray luminosity of up to 0.7 × 1039 erg s−1. The observed periodicity of 3.62 h, derived from eclipse timing, is interpreted as the orbital period of the system. It has been suggested that the system is a low-mass helium star with a lower-mass compact companion. If this idea is correct, then CXOU J121538.2+361921 will evolve into a double neutron star, a binary consisting of a radio pulsar and another neutron star. In this study we investigate this possibility further. We find that the X-ray luminosity is consistent with super-Eddington accretion in a helium star-neutron star binary. The binary is in a state of mass transfer which is initiated when the helium-star donor is at the helium shell burning stage. A donor star with a current mass in the range of around 2.2–3.6 M⊙ is required to explain the observed orbital period. Helium stars in this mass range are massive enough to collapse in a supernova explosion, making CXOU J121538.2+361921 the immediate progenitor of a double neutron star.
The X-ray afterglow flat segment in short GRB 051221A: Energy injection from a millisecond magnetar?
Authors: Fan Yi-Zhong , Xu Dong
Published: August 2006

The flat segment, lasting ∼104 s, in the X-ray afterglow of GRB 051221A represents the first clear case of strong energy injection in the external shock of a short gamma-ray burst (GRB) afterglow. In this work, we show that a millisecond pulsar with a dipole magnetic field ∼1014 Gauss could well account for that energy injection. The good quality X-ray flat segment thus suggests that the central engine of this short burst may be a millisecond magnetar.
Economic Theory and Political Reality: Managed Competition and U.S. Health Policy
Authors: Kreier Rachel
Published: August 2006

During the 1992 campaign, candidate Bill Clinton made the strategic decision to embrace many aspects of an economic model called “managed competition” in his approach to health‐care reform. Managed competition ideas did not die when Clinton’s health plan expired. Instead, they informed the 1997 expansion of a demonstration project into the Medicare + Choice program. Today, the Medicare + Choice legacy lives on in the Medicare Advantage and prescription drug programs created by the Medicare Prescription Drug, Improvement and Modernization Act of 2003. Shortcomings of the managed competition approach received little public attention during the debate over the Medicare Modernization Act, despite the fact that the record of Medicare + Choice is disappointing in a number of respects. There are serious questions about the ability of the managed competition approach to control costs and achieve equitable access to high‐quality care. Nevertheless, the approach remains influential largely because of political considerations.
Consequential Apoptosis in the Cerebellum Following Injury to the Developing Rat Forebrain
Authors: Taylor Deanna L. , Joashi Umesh C. , Sarraf Catherine , Edwards A. David , Mehmet Huseyin
Published: August 2006

In focal brain lesions, alterations in blood flow and cerebral metabolism can be detected in brain areas remote from the primary injury. The cellular consequences of this phenomenon, originally termed diaschisis, are not fully understood. Here, we report that in two distinct models of forebrain injury, neuronal death in the cerebellum, a site distant to the primary injury, results as consequence of neuronal loss in the forebrain. Fourteen‐day‐old rats were subjected to unilateral forebrain injury, achieved by either hypoxia‐ischemia (right carotid artery ligation and hypoxia) or direct needle injury to brain tissue. At defined times after injury, the presence of apoptosis was investigated by cell morphology, in situ end labeling, electron microscopy and poly‐ADP‐ribose polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia‐ischemia increased apoptosis in the internal granular and Purkinje cell layers of the cerebellum, a site distant to that of the primary injury. The number of apoptotic cells in the cerebellum was significantly related to cell death in the hippocampus. Similarly, direct needle injury to the forebrain resulted in extensive apoptotic cell death in the cerebellum. These results emphasize the intimate relationship between defined neuronal populations in relatively distant brain areas and suggest a cellular basis for diaschisis.
Spinal Cord Gray Matter Demyelination in Multiple Sclerosis—A Novel Pattern of Residual Plaque Morphology
Authors: Gilmore Christopher P. , Bö Lars , Owens Trudy , Lowe James , Esiri Margaret M. , Evangelou Nikos
Published: August 2006

The extent and pattern of gray matter (GM) demyelination in the spinal cord in multiple sclerosis (MS) has not been examined in detail. Human autopsy material was obtained from 36 MS cases and 12 controls. Transverse sections were taken from five levels of the spinal cord (upper cervical, lower cervical, upper thoracic, lower thoracic and lumbar levels) and the extent of GM and white matter (WM) demyelination evaluated using proteolipid protein immunohistochemistry (IHC). The proportion of the GM that was demyelinated (33%) was significantly greater than the proportion of demyelinated WM (20%) (P < 0.0001). Similarly, demyelination was more extensive in the GM than in the WM at each of the five cord levels. The extent of GM demyelination was not significantly different between the five cord levels while WM demyelination was greatest at the upper cervical level. Morphologically, the borders of a proportion of the GM plaques show a strict respect for the GM/WM boundary. We demonstrate that extensive demyelination occurs in the GM of the spinal cord in MS. Myelin protein IHC reveals a novel pattern of residual plaque morphology challenging previous work suggesting that MS plaques display a total disregard for anatomical boundaries.
Intrauterine Exposure to Dexamethasone Impairs Proliferation But Not Neuronal Differentiation in the Dentate Gyrus of Newborn Common Marmoset Monkeys
Authors: Tauber Simone C. , Schlumbohm Christina , Schilg Lenka , Fuchs Eberhard , Nau Roland , Gerber Joachim
Published: August 2006

Glucocorticoids applied prenatally alter birth weight and the maturation of the lungs. Moreover, glucocorticoids impair neuronal proliferation and differentiation in the hippocampal dentate gyrus. In the present study proliferation and neuronal differentiation in the dentate gyrus were studied in newborn common marmoset monkeys which were intrauterinely exposed to the synthetic glucocorticoid dexamethasone (DEX). Pregnant marmoset monkeys received DEX (5 mg/kg body weight) daily either during early (days 42–48) or late (days 90–96) pregnancy. In the hippocampi of newborn monkeys immunohistochemistry was performed with markers of proliferation (Ki‐67), apoptosis (in situ tailing) as well as early and late neuronal differentiation (calretinin and calbindin). Both after early and late intrauterine exposure to DEX, proliferation of dentate gyrus cells was significantly decreased (P < 0.05). The density of apoptotic neurons was not altered by DEX treatment. Quantification of calretinin‐ and calbindin‐immunoreactive neurons showed no significant differences between DEX‐exposed and control animals. In conclusion, the proliferation of putative precursor cells but not the differentiation into mature cells was impaired in the dentate gyrus of newborn marmosets exposed intrauterinely to DEX.
Spinocerebellar Ataxia Type 3 (SCA3): Thalamic Neurodegeneration Occurs Independently from Thalamic Ataxin‐3 Immunopositive Neuronal Intranuclear Inclusions
Authors: Rüb Udo , De Vos Rob A.I. , Brunt Ewout R. , Sebestény Tamás , Schöls Ludger , Auburger Georg , Bohl Jürgen , Ghebremedhin Estifanos , Gierga Kristin , Seidel Kay , Den Dunnen Wilfred , Heinsen Helmut , Paulson Henry , Deller Thomas
Published: August 2006

In the last years progress has been made regarding the involvement of the thalamus during the course of the currently known polyglutamine diseases. Although recent studies have shown that the thalamus consistently undergoes neurodegeneration in Huntington’s disease (HD) and spinocerebellar ataxia type 2 (SCA2) it is still unclear whether it is also a consistent target of the pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we studied the thalamic pathoanatomy and distribution pattern of ataxin‐3 immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed and genetically confirmed SCA3 patients and carried out a detailed statistical analysis of our findings. During our pathoanatomical study we disclosed (i) a consistent degeneration of the ventral anterior, ventral lateral and reticular thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and inferior and lateral subnuclei of the pulvinar in the majority of these SCA3 patients; and (iii) a degeneration of the ventral posterior medial and lateral posterior thalamic nuclei, the lateral geniculate body and some of the limbic thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI in all of the thalamic nuclei of all of our SCA3 patients. According to our statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin‐3 immunopositive thalamic NI was not associated with the individual length of the CAG‐repeats in the mutated SCA3 allele, the patients age at disease onset and the duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the occurrence of ataxin‐3 immunopositive thalamic NI. This lack of correlation may suggest that ataxin‐3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3.
Sensory elements within the circular muscle are essential for mechanotransduction of ongoing peristaltic reflex activity in guinea‐pig distal colon
Authors: Spencer Nick J. , Dickson Eamonn J. , Hennig Grant W. , Smith Terence K.
Published: August 2006

We have recently identified a population of mechanosensory myenteric S‐interneurons in the distal colon of guinea‐pigs. However, the role of the longitudinal (LM) and circular muscle (CM) in transducing these mechanosensory signals into enteric reflexes is unclear. In this study, we have investigated whether the LM or CM layer is necessary for activation of ascending excitatory and descending inhibitory neuronal pathways by static stretch of the paralysed isolated guinea‐pig distal colon. Simultaneous intracellular recordings were made from pairs of CM cells at either end of isolated sheet preparations of distal colon that were devoid of mucosa and submucous plexus; and were maintained under circumferential stretch. In the presence of nifedipine (1 μm), an ongoing discharge of excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs) were recorded simultaneously at the oral and anal ends of the preparation. When the LM was sharp dissected off the myenteric plexus, the synchronized discharge of ascending EJPs and descending IJPs in the CM layer was unaffected. In contrast, when the majority of CM was sharp dissected off the myenteric plexus, ongoing neural activity was absent, or substantially decreased in both the LM and CM. In these preparations, immunohistochemical staining, together with transmural electrical stimuli confirmed that the myenteric plexus was always present and intact in these preparations. When full‐thickness strips of CM were removed from progressively longer lengths of myenteric plexus, a graded reduction in the correlation of coordinated oral EJPs and anal IJPs occurred. However, removing ∼40% of the thickness of CM layer from the entire preparation did not significantly disrupt, nor reduce the degree of correlation between oral EJPs and anal IJPs, suggesting that critical sensory elements did not lie adjacent to the submucosal plexus. It is concluded that mechanosensory transmission that underlies repetitive firing of ascending excitatory and descending inhibitory neuronal pathways is critically dependent upon sensory elements within the CM layer. These elements are likely to activate stretch‐sensitive interneurons in the myenteric plexus. No evidence was found to suggest that the connectivity between the LM and the myenteric plexus was required for mechanotransduction.
The N‐terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels
Authors: Fang Kun , Csanády László , Chan Kim W.
Published: August 2006

ATP‐sensitive potassium (KATP) channels comprise four pore‐forming Kir6 and four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP‐binding cassette protein, associates with Kir6 through its N‐terminal transmembrane domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been hypothesized that these changes are conferred by TMD0. Exploiting the fact that the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) KATP channels show different gating behaviours, we have tested this hypothesis by comparing the intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Δ26) co‐expressed with SUR1, S1‐TMD0, SUR2A and S2‐TMD0 at −40 and −100 mV (S is an abbreviation for SUR; TMD0/Kir6.2Δ26, but not TMD0/Kir6.2, can exit the endoplastic reticulum and reach the cell membrane). Single‐channel kinetic analyses revealed that the mean burst and interburst durations are shorter for TMD0/Kir6.2Δ26 than for the corresponding SUR channels. No differences were found between the two TMD0 channels. We further demonstrated that in isolation even TMD0‐L0 (SUR truncated after L0) cannot confer the wild‐type intrinsic gating to Kir6.2Δ26 and that swapping L0 (SUR truncated after L0)between SUR1 and SUR2A only partially exchanges their different intrinsic gating. Therefore, in addition to TMD0, L0 and the core domain also participate in determining the intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the different gating patterns of full‐length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context.
Active hair bundle movements in auditory hair cells
Authors: Fettiplace Robert
Published: August 2006

The frequency selectivity of mammalian hearing depends on not only the passive mechanics of the basilar membrane but also an active amplification of the mechanical stimulus by the cochlear hair cells. The common view is that amplification stems from the somatic motility of the outer hair cells (OHCs), changes in their length impelled by voltage‐dependent transitions in the membrane protein prestin. Whether this voltage‐controlled mechanism, whose frequency range may be limited by the membrane time constant, has the band width to cover the entire auditory range of mammals is uncertain. However, there is ample evidence for an alternative mode of force generation by hair cells of non‐mammals, such as frogs and turtles, which probably lack prestin. The latter process involves active motion of the hair bundle underpinned by conformational changes in the mechanotransducer (MT) channels and activation of one or more isoforms of myosin. This review summarizes evidence for active hair bundle motion and its connection to MT channel adaptation. Key factors for the hair bundle motor to play a role in the mammalian cochlea include the size and speed of force production.
The Effect of Self-Assembled Monolayers on Interfacial Fracture
Authors: Mello Alberto W. , Liechti Kenneth M.
Published: August 2006

This paper describes a series of experiments and analyses that were used to examine crack growth near sapphire/epoxy interfaces. Adhesion of the epoxy to the sapphire was enhanced by coating the sapphire with mixtures of two silane coupling agents that form self-assembled monolayers. A new biaxial loading device was used to conduct a series of mixed-mode fracture experiments. Crack opening interferometry, atomic force microscopy, and angle-resolved X-ray photoelectron spectroscopy allowed cohesive zone sizes, fracture surface topographies, and loci of fracture to be established. The experiments were complemented by finite element analyses that accounted for the rate- and pressure-dependent yielding of the epoxy. The analyses also made use of traction-separation laws to represent the various interphases that were produced by the mixed monolayers. The intrinsic toughness (defined as the area underneath the traction-separation curve) of the bare sapphire interfaces was independent of mode-mix and lower than values from previous experiments with glass/epoxy and quartz/epoxy specimens. The increase in overall toughness with mode-mix was completely accounted for by viscoplastic dissipation in the epoxy outside the cohesive zone. The minimum toughness of the coated sapphire interfaces was about five times higher than the mode-mix independent intrinsic toughness of the uncoated specimens. The increase in overall toughness with mode-mix was almost completely accounted for by increases in the intrinsic toughness as the traction-separation law varied with mode-mix. As a result, viscoplastic dissipation outside the cohesive zone was minimal. Atomic force fractography and X-ray photoelectron spectroscopy indicated that the crack growth mechanisms and the loci of fracture in the coated and uncoated specimens were quite different.
A Hybrid Continuum-Molecular Analysis of Interfacial Force Microscope Experiments on a Self-Assembled Monolayer
Authors: Wang Mingji , Liechti Kenneth M. , Srinivasan Vibha , White John M. , Rossky Peter J. , Stone Matthew T.
Published: August 2006

Nanoindentation experiments were performed on a defect-free, molecular self-assembled monolayer of octadecyltrichlorosilane (OTS) on silicon using an interfacial force microscope (IFM). The IFM provided repeatable and elastic force profiles corresponding to the adhesive and compressive response of these 2.5nm thick monolayers. As a first step in the analysis of the force profiles, the OTS was assumed to be linearly elastic and isotropic, and adhesive interactions were accounted for via a cohesive zone model. However, the assumption of linearity gave rise to force profiles that did not match the measurements. As a result, the mechanical behavior of the OTS was extracted from molecular-dynamics simulations and represented as a hypoelastic material, which, when used in finite element analyses of the IFM experiments, was able to fully reproduce the force profiles. This suggests that the continuum representation of the mechanical and adhesive behavior of self-assembled monolayers may be directly obtained from molecular analyses.
On the Crush Worthiness of a Laterally Confined Bar Under Axial Compression
Authors: Chai Herzl
Published: August 2006

A combined experimental∕analytical work is carried out to elucidate the energy absorption potential of laterally confined bars under monotonically increasing edge displacement. The thickness t and length L of the bar, as well as the wall-to-wall separation distance, h, are systematically varied. Real-time observations show that the deformation of the bar is characterized by progressive buckling and folding, with the fully compacted material exhibiting repetitious cell unit whose wavelength approximately equals four times the bar thickness. The specific crush energy is little sensitive to the thickness of the bar but strongly varies with t∕h, the “volume fraction” of the structure, attaining a maximum when t∕h≈0.5. The main sources for energy dissipation are simple compression, plate folding and friction between the bar and the constraining walls, the latter of which dominates for L∕t>10. The experimental data are found to be well predicted by simple analytic expressions derived from limit plasticity analysis and incompressible material behavior. The simple configuration studied may shed light on the behavior of more complex structures such as honeycombs, foams, and thin-walled tubes, and may serve as a basis for multi-layer design possessing improved crush energy.
On the Crushing Stress of Open Cell Foams
Authors: Gong Lixin , Kyriakides Stelios
Published: August 2006

The compressive response of many foams is characterized by an initial linearly elastic regime which is terminated by instability. For open cell foams instability leads to localized buckling and collapse of zones of cells. Local collapse in these zones is terminated by contact between cell ligaments. In the process collapse spreads to neighboring cells hitherto intact. The spreading of collapse occurs at a well-defined load plateau and continues until most of the cells are thus affected when the material response regains stiffness once more. This type of three-regime compressive response was reproduced numerically by idealizing such foams to be assemblages of space-filling Kelvin cells. The onset of instability involves a long wavelength mode. It has been established by considering a fully periodic column of cells tall enough to accommodate this mode. The crushing response has been evaluated by considering finite size microsections which allow localized deformation to develop. This paper shows that the crushing stress can also be established from the local response of the fully periodic column of cells through an energy argument leading to a Maxwell-type construction.
Computational Fracture Mechanics Analysis of Truck Tire
Durability
Authors: Zhong X. Allan
Published: August 2006

A three-dimensional fracture mechanics model is formulated to study fatigue crack growth and durability in tires. The application of this model in a radial medium truck tire reveals fracture characteristics of belt edge cracks and helps to explain mechanical and material changes in the tire subject to indoor accelerated durability tests. Along with a proprietary fatigue crack growth law, a fracture mechanics based durability analysis methodology is developed and successfully applied to rank durability of tires with different constructions or different rubber materials.
An Anisotropic Hyperelastic Constitutive Model With Fiber-Matrix Shear Interaction for the Human Annulus Fibrosus
Authors: Peng X. Q. , Guo Z. Y. , Moran B.
Published: August 2006

Based on fiber reinforced continuum mechanics theory, an anisotropic hyperelastic constitutive model for the human annulus fibrosus is developed. A strain energy function representing the anisotropic elastic material behavior of the annulus fibrosus is additively decomposed into three parts nominally representing the energy contributions from the matrix, fiber and fiber-matrix shear interaction, respectively. Taking advantage of the laminated structure of the annulus fibrosus with one family of aligned fibers in each lamella, interlamellar fiber-fiber interaction is eliminated, which greatly simplifies the constitutive model. A simple geometric description for the shearing between the fiber and the matrix is developed and this quantity is used in the representation of the fiber-matrix shear interaction energy. Intralamellar fiber-fiber interaction is also encompassed by this interaction term. Experimental data from the literature are used to obtain the material parameters in the constitutive model and to provide model validation. Determination of the material parameters is greatly facilitated by the partition of the strain energy function into matrix, fiber and fiber-matrix shear interaction terms. A straightforward procedure for computation of the material parameters from simple experimental tests is proposed.
A Comparison of X-Ray Microdiffraction and Coherent Gradient Sensing in Measuring Discontinuous Curvatures in Thin Film: Substrate Systems
Authors: Brown Michal A. , Park Tae-Soon , Rosakis Ares , Ustundag Ersan , Huang Young , Tamura Nobumichi , Valek Bryan
Published: August 2006

The coherent gradient sensor (CGS) is a shearing interferometer which has been proposed for the rapid, full-field measurement of deformation states (slopes and curvatures) in thin film-wafer substrate systems, and for the subsequent inference of stresses in the thin films. This approach needs to be verified using a more well-established but time-consuming grain orientation and stress measurement tool, X-ray microdiffraction (XRD). Both CGS and XRD are used to measure the deformation state of the same W film/Si wafer at room temperature. CGS provides a global, wafer-level measurement of slopes while XRD provides a local micromeasurement of lattice rotations. An extreme case of a circular Si wafer with a circular W film island in its center is used because of the presence of discontinuous system curvatures across the wafer. The results are also compared with a theoretical model based on elastic plate analysis of the axisymmetric biomaterial film-substrate system. Slope and curvature measurements by XRD and by CGS compare very well with each other and with theory. The favorable comparison demonstrates that wafer-level CGS metrology provides a quick and accurate alternative to other measurements. It also demonstrates the accuracy of plate theory in modeling thin film-substrate systems, even in the presence of curvature discontinuities