bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of low frequency electromagnetic field on solidification of 7050 aluminium alloy during hot top casting
Authors: Wang X. J. , Zhao Z. H. , Zuo Y. B. , Zhu Q. F. , Qu F. , Cui J. Z.
Published: December 2008

On the basis of conventional hot top casting, low frequency electromagnetic field is applied during conventional hot top casting process. Effects of low frequency electromagnetic field on cold fold, macrostructure, microstructure and sump shape have been studied. The experimental results show that with the application of the low frequency electromagnetic filed, the as cast structure has been refined, the depth of cold fold is decreased, the upstream conduction distance becomes long, and the sump becomes shallow. The reasons for the low frequency electromagnetic field refining the structure of the ingot, making the upstream conduction distance long and the sump shallow were summarised.
Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers
Authors: Ahlquist Terje , Lind Guro E , Costa Vera L , Meling Gunn I , Vatn Morten , Hoff Geir S , Rognum Torleiv O , Skotheim Rolf I , Thiis-Evensen Espen , Lothe Ragnhild A
Published: December 2008

Background

Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential.

The methylation status of eleven genes (ADAMTS1,CDKN2A,CRABP1,HOXA9,MAL,MGMT,MLH1,NR3C1,PTEN,RUNX3, andSCGB3A1) was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI),BRAF-,KRAS-, andTP53mutation status.

Results

The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters ofADAMTS1,MAL, andMGMTwere frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. HypermethylatedCRABP1, MLH1,NR3C1,RUNX3, andSCGB3A1were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutatedBRAFwere associated with samples harboring hypermethylation of several target genes.

Conclusion

MethylatedADAMTS1,MGMT, andMALare suitable as markers for early tumor detection.
Neural correlates of executive function and working memory in the ‘at-risk mental state’
Authors: Broome Matthew R. , Matthiasson Pall , Fusar-Poli Paolo , Woolley James B. , Johns Louise C. , Tabraham Paul , Bramon Elvira , Valmaggia Lucia , Williams Steven C. R. , Brammer Michael J. , Chitnis Xavier , McGuire Philip K.
Published: December 2008

Background

People with prodromal symptoms have a very high risk of developing psychosis.

Aims

To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability.

Method

Cross-sectional comparison of regional activation in individuals with an ‘at-risk mental state’ (at-risk group:n=17), patients with first-episode schizophreniform psychosis (psychosis group:n=10) and healthy volunteers (controls:n=15) during an overt verbal fluency task and anN-back working memory task.

Results

A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during theN-back task.

Conclusions

The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.
Psychopathy traits in adolescents with childhood attention-deficit hyperactivity disorder
Authors: Fowler Tom , Langley Kate , Rice Frances , Whittinger Naureen , Ross Kenny , Goozen Stephanie van , Owen Michael J. , O'Donovan Michael C. , van den Bree Marianne B. M. , Thapar Anita
Published: December 2008

Background

Children with attention-deficit hyperactivity disorder (ADHD) are thought to be at higher risk of psychopathy. Early biological and social adversity may contribute to this risk.

Aims

To examine psychopathy traits in ADHD.

Method

In a sample of children with ADHD who had reached adolescence, total psychopathy and ‘emotional-dysfunction’ scores (e.g. callousness, lack of affect) were assessed using the Hare Psychopathy Checklist–Youth Version.

Results

A total of 156 (79%) eligible families participated. Total psychopathy and emotional-dysfunction scores were elevated in comparison to published UK norms but none scored in the clinical range for psychopathy. Adjusting for associated conduct problems, total psychopathy scores were associated with maternal smoking during pregnancy, emotional-dysfunction scores were associated with birth complications, and neither was associated with family adversity.

Conclusions

Children with ADHD show psychopathy traits but are not ‘psychopaths’. Early adversity, indexed by pre- or perinatal adversity but not family factors, appears to be associated.
Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials
Authors: Geddes John R. , Calabrese Joseph R. , Goodwin Guy M.
Published: December 2008

Background

There is uncertainty about the efficacy of lamotrigine in bipolar depressive episodes.

Aims

To synthesise the evidence for the efficacy of lamotrigine in bipolar depressive episodes.

Method

Systematic review and meta-analysis of individual patient data from randomised controlled trials comparing lamotrigine with placebo.

Results

Individual data from 1072 participants from five randomised controlled trials were obtained. More individuals treated with lamotrigine than placebo responded to treatment on both the Hamilton Rating Scale for Depression (HRSD) (relative risk (RR)=1.27, 95% CI 1.09–1.47, P=0.002) and Montgomery– åsberg Depression Rating Scale (MADRS) (RR=1.22, 95% CI 1.06–1.41, P=0.005). There was an interaction (P=0.04) by baseline severity of depression: lamotrigine was superior to placebo in people with HRSD score >24 (RR=1.47, 95% CI 1.16–1.87, P=0.001) but not in people with HRSD score 24 (RR=1.07, 95% CI 0.90–1.27, P=0.445).

Conclusions

There is consistent evidence that lamotrigine has a beneficial effect on depressive symptoms in the depressed phase of bipolar disorder. The overall pool effect was modest, although the advantage over placebo was larger in more severely depressed participants.
Developing a care pathway for advance decisions and powers of attorney: qualitative study
Authors: Bisson Jonathan I. , Hampton Victoria , Rosser Anne , Holm Søren
Published: December 2008

Background

The Mental Capacity Act for England and Wales empowers individuals to plan ahead for when they may lack capacity.

Aims

To develop a care pathway for advance decisions and powers of attorney using Huntington's disease as an exemplar.

Method

Qualitative study using in-depth individual interviews with service users and carers, and focus groups with professionals. Inductive qualitative analysis was used to develop themes to construct a care pathway that was then piloted and further evaluated to achieve a final pathway.

Results

A care pathway was developed that incorporated an early introduction through a formal education session and a minimum of two sessions separated by at least 2 weeks before advance decision completion. Optimal delivery of this intervention requires significant clinical and administrative commitment.

Conclusions

We have developed a simple, easy-to-follow care pathway that was acceptable to users and providers.
Effect of 7 July 2005 terrorist attacks in London on suicide in England and Wales
Authors: Salib Emad , Cortina-Borja Mario
Published: December 2008

Background

A reduction in suicide in England and Wales has been reported after the attacks of 11 September 2001 in the USA. It may be plausible therefore to expect a much greater impact on suicide in the UK in response to the events of 7 July 2005, caused by the first suicide terrorist attack by Islamic extremists on British soil.

Aims

To examine the effect of the 7 July 2005 terrorist attacks in London on suicide rates in England and Wales.

Method

Analysis of number of suicide (ICD–10 codes X60–X84) and undetermined injury deaths (ICD–10 codes Y10–Y34) reported in England and Wales in the 12 weeks before and after 7 July 2005. We used Shewhart Control Charts based on Poisson rates to explore adjusted daily and weekly suicide rates and rate differences with respect to 7 July 2005.

Results

A brief but significant reduction in daily suicide rate was observed a few days after the terrorist attack in London on 7 July 2005. Further reduction was also observed on the 21 July 2005, coinciding with the second wave of attacks. No similar reduction in suicide was seen during the same period in the previous 4 years. Poisson regression models with indicator variables for each day in July 2005 revealed a reduction of 40% of the expected daily rate for these 2 days only. We found no evidence of any longer-term effect on suicide.

Conclusions

The study findings are contrary to our expectation and only weakly support Durkheim's theory that periods of national threat lower the suicide rate through the impact on social cohesion. It is possible that previous experience of IRA terrorism in the UK may have limited the effect of the 7 July 2005 attacks on suicide in England and Wales. The shock value of suicide terrorism and its psychological potency appear to diminish over time as the tactic becomes overused.
Aripiprazole monotherapy in acute mania: 12-week randomised placebo- and haloperidol-controlled study
Authors: Young Allan H. , Oren Dan A. , Lowy Adam , McQuade Robert D. , Marcus Ronald N. , Carson William H. , Spiller Nina H. , Torbeyns Anne F. , Sanchez Raymond
Published: December 2008

Background

Well-tolerated and effective therapies for bipolar mania are required.

Aims

To evaluate the efficacy and tolerability of aripiprazole as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes.

Method

Patients were randomised to double-blind aripiprazole (15 or 30 mg/day; n=167) placebo (n=153) or haloperidol (5–15 mg/day, n=165) for 3 weeks (trial registration NCT00097266). Aripiprazole- and haloperidol-treated patients remained on masked treatment for 9 additional weeks.

Results

Mean change in Young Mania Rating Scale Total score (primary end-point) at week 3 was significantly greater with aripiprazole (–12.0; P<0.05) and haloperidol (–12.8; P<0.01) than with placebo (–9.7). Improvements were maintained to week 12 for aripiprazole (–17.2) and haloperidol (–17.8). Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (53.3% v. 23.5%).

Conclusions

Clinical improvements with aripiprazole were sustained to week 12. Aripiprazole was generally well tolerated.
Family participation in treatment, post-discharge appointment and medication adherence at a Nigerian psychiatric hospital
Authors: Adeponle Ademola B. , Thombs Brett D. , Adelekan Moruf L. , Kirmayer Laurence J.
Published: December 2008

In low-income countries, clinicians must seek strategies to improve treatment adherence that are non-resource intensive and easily integrated into existing treatment structures. We conducted a prospective observational cohort study to investigate the relationship of family engagement in treatment during hospitalisation with post-discharge appointment and medication adherence in 81 patients from a Nigerian psychiatric hospital. After controlling for gender, diagnosis, mental state at discharge, and marital status, family involvement was significantly associated with appointment (P=0.047) but not medication adherence (P=0.590). Studies are needed to determine whether interventions based on engaging families in treatment can improve post-discharge adherence in this setting.
Excess mortality, causes of death and prognostic factors in anorexia nervosa
Authors: Papadopoulos Fotios C. , Ekbom Anders , Brandt Lena , Ekselius Lisa
Published: December 2008

Background

Anorexia nervosa is a mental disorder with high mortality.

Aims

To estimate standardised mortality ratios (SMRs) and to investigate potential prognostic factors.

Method

Six thousand and nine women who had in-patient treatment for anorexia nervosa were followed-up retrospectively using Swedish registers.

Results

The overall SMR for anorexia nervosa was 6.2 (95% CI 5.5– 7.0). Anorexia nervosa, psychoactive substance use and suicide had the highest SMR. The SMR was significantly increased for almost all natural and unnatural causes of death. The SMR 20 years or more after the first hospitalisation remained significantly high. Lower mortality was found during the last two decades. Younger age and longer hospital stay at first hospitalisation was associated with better outcome, and psychiatric and somatic comorbidity worsened the outcome.

Conclusions

Anorexia nervosa is characterised by high lifetime mortality from both natural and unnatural causes. Assessment and treatment of psychiatric comorbidity, especially alcohol misuse, may be a pathway to better long-term outcome.
Sphingosine Kinase as an Oncogene: Autocrine Sphingosine 1-Phoshate Modulates ML-1 Thyroid Carcinoma Cell Migration by a Mechanism Dependent on Protein Kinase C-α and ERK1/2
Authors: Bergelin N. , Blom T. , Heikkilä J. , Löf C. , Alam C. , Balthasar S. , Slotte J. P. , Hinkkanen A. , Törnquist K.
Published: December 2008

Sphingosine 1-phosphate (S1P) induces migration of the human thyroid follicular carcinoma cell line ML-1 by activation of S1P1 and S1P3 receptors, Gi proteins, and the phosphatidylinositol 3-kinase-Akt pathway. Because sphingosine kinase isoform 1 (SK) recently has been implicated as an oncogene in various cancer cell systems, we investigated the functions of SK in the migration, proliferation and adhesion of the ML-1 cell line. SK overexpressing ML-1 cells show an enhanced secretion of S1P, which can be attenuated, by inhibiting SK activity and a multidrug-resistant transport protein (ATP-binding cassette transporter). Furthermore, overexpression of SK enhances serum-induced migration of ML-1 cells, which can be attenuated by blocking ATP-binding cassette transporter and SK, suggesting that the migration is mediated by autocrine signaling through secretion of S1P. Inhibition of protein kinase Cα, with both small interfering RNA (siRNA) and small molecular inhibitors attenuates migration in SK overexpressing cells. In addition, SK-overexpressing cells show an impaired adhesion, slower cell growth, and an up-regulation of ERK1/2 phosphorylation, as compared with cells expressing a dominant-negative SK. Taken together, we present evidence suggesting that SK enhances migration of ML-1 cells by an autocrine mechanism and that the S1P-evoked migration is dependent on protein kinase Cα, ERK1/2, and SK.
Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice
Authors: Ding Jun , Gao Yan , Zhao Jing , Yan Hong , Guo Shi-ying , Zhang Qin-xian , Li Ling-song , Gao Xiang
Published: December 2008

Heterozygosity for the Pax6 allele is associated with impaired glucose tolerance in humans. With a Pax6 mutant mouse model, we found many of the metabolic abnormalities were consistent with the effects of down-regulating the expression of glucagon-like peptide 1 (GLP-1). In addition to impaired glucose tolerance, adult heterozygous mutant mice (Pax6m/+) secreted less insulin responding to glucose and arginine administration compared with control mice. Moreover, Pax6m/+ mice showed increased food intake compared with control mice, although they were resistant to diet-induced fat accumulation. Indeed, levels of circulating GLP-1 and intestinal transcription of Gcg/Proglucagon were dramatically reduced in Pax6m/+ mice. Mutated Pax6 also failed to activate the Gcg/Proglucagon promoter by in vitro transfection assay. Finally, administering the GLP-1 receptor agonist exendin-4 to Pax6m/+ mice largely reversed their abnormal food intake, glycemic excursion, and insulin secretion. Our studies suggested that disruption of metabolic homeostasis mainly caused by Pax6 haploinsufficiency was mainly mediated by down-regulation of GLP-1. Administration of exendin-4 may be a useful therapy in humans with a similar mutation.
Epidermal Growth Factor Receptor Pathway Substrate 8 Is Overexpressed in Human Pituitary Tumors: Role in Proliferation and Survival
Authors: Xu Mei , Shorts-Cary Lynnette , Knox Aaron J. , Kleinsmidt-DeMasters B , Lillehei Kevin , Wierman Margaret E.
Published: December 2008

Based on prior work showing that human pituitary tumors overexpress epidermal and fibroblast growth factor receptors, we hypothesized that downstream components of growth factor signaling pathways may also be dysregulated. Epidermal growth factor pathway substrate number 8 (Eps8) was identified as a transcript overexpressed (5.9-fold) in human pituitary tumors compared with normal pituitary by DNA microarrays. Eps8 mRNA up-regulation was confirmed by semiquantitative RT-PCR. Immunoblot analysis showed that Eps8 protein levels and its downstream target phosphorylated ERK were also up-regulated in human pituitary tumors. Stable overexpression of Eps8 in LβT2 gonadotrope pituitary cells augmented colony formation in soft agar at d 21. Eps8 cells proliferated more robustly compared with controls in growth factor replete as well as growth-restricted conditions. In addition, the Eps8 overexpressing cells were protected from serum withdrawal-induced apoptosis compared with controls as assessed by caspase-3 cleavage. Epidermal growth factor activated a robust amplification of ERK and modest up-regulation of Akt in Eps8-overexpressing pituitary cells compared with vector controls. MAPK kinase inhibition or silencing of Eps8 blunted the proliferation of the cells in response to growth factor stimulation. Blockade of the phosphatidylinositol 3-kinase pathway or silencing of Eps8 resulted in a loss of the Eps8 protection from growth factor withdrawal-induced apoptosis. Together these data support a role of Eps8 in amplifying growth factor receptor signaling in human pituitary tumors to promote proliferation and cell survival.
SUMO-Specific Protease 1 (SENP1) Reverses the Hormone-Augmented SUMOylation of Androgen Receptor and Modulates Gene Responses in Prostate Cancer Cells
Authors: Kaikkonen Sanna , Jääskeläinen Tiina , Karvonen Ulla , Rytinki Miia M. , Makkonen Harri , Gioeli Daniel , Paschal Bryce M. , Palvimo Jorma J.
Published: December 2008

The acceptor sites for small ubiquitin-like modifier (SUMO) are conserved in the N-terminal domains of several nuclear receptors. Here, we show that androgens induce rapid and dynamic conjugation of SUMO-1 to androgen receptor (AR). Nuclear import of AR is not sufficient for SUMOylation, because constitutively nuclear apo-ARs or antagonist-bound ARs are only very weakly modified by SUMO-1 in comparison with agonist-bound ARs. Of the SUMO-specific proteases (SENP)-1, -2, -3, -5, and -6, only SENP1 and SENP2 are efficient in cleaving AR-SUMO-1 conjugates in intact cells and in vitro. Both SENP1 and -2 are nuclear and found at sites proximal to AR. Their expression promotes AR-dependent transcription, but in a promoter-selective fashion. SENP1 and -2 stimulated the activity of holo-AR on compound androgen response element-containing promoters. The effects of SENP1 and -2 on AR-dependent transcription were dependent on catalytic activity and required intact SUMO acceptor sites in AR, indicating that their coactivating effects are mainly due to their direct isopeptidase activity on holo-AR. In prostate cancer cells, ectopic expression of SENP1, but not that of SENP2, increased the transcription activity of endogenous AR. Silencing of SENP1 attenuated the expression of several AR target genes and blunted androgen-stimulated growth of LNCaP cells. Our results indicate that SENP1 reverses the ligand-induced SUMOylation of AR and helps fine tune the cellular responses to androgens in a target promoter-selective manner.
Linking integrin conformation to function
Authors: Askari Janet A. , Buckley Patrick A. , Mould A. Paul , Humphries Martin J.
Published: December 2008

Integrins are αβ heterodimeric adhesion receptors that relay signals bidirectionally across the plasma membrane between the extracellular matrix and cell-surface ligands, and cytoskeletal and signalling effectors. The physical and chemical signals that are controlled by integrins are essential for intercellular communication and underpin all aspects of metazoan existence. To mediate such diverse functions, integrins exhibit structural diversity, flexibility and dynamism. Conformational changes, as opposed to surface expression or clustering, are central to the regulation of receptor function. In recent years, there has been intense interest in determining the three-dimensional structure of integrins, and analysing the shape changes that underpin the interconversion between functional states. Considering the central importance of the integrin signalling nexus, it is perhaps no surprise that obtaining this information has been difficult, and the answers gained so far have been complicated. In this Commentary, we pose some of the key remaining questions that surround integrin structure-function relationships and review the evidence that supports the current models.
Mice that lack activity of αvβ6- and αvβ8-integrins reproduce the abnormalities ofTgfb1- andTgfb3-null mice
Authors: Aluwihare Poshala , Mu Zhenyu , Zhao Zhicheng , Yu Dawen , Weinreb Paul H. , Horan Gerald S. , Violette Shelia M. , Munger John S.
Published: December 2008

The arginine-glycine-aspartate (RGD)-binding integrins αvβ6 and αvβ8 activate latent TGFβ1 and TGFβ3 in vivo, but it is uncertain whether other RGD-binding integrins such as integrins αvβ5 and αvβ3 activate these TGFβ isoforms. To define the combined role of αvβ6- and αvβ8-integrin in TGFβ activation, we analyzed mice lacking function of both integrins by means of gene deletion and/or pharmacologic inhibition. Most Itgb6–/–;Itgb8–/– embryos die at mid-gestation; those that survive develop cleft palate–as observed in Tgfb3–/– mice. Itgb8–/– mice treated with an anti-αvβ6-integrin antibody develop severe autoimmunity and lack Langerhans cells–similar to Tgfb1-null mice. These results support a model in which TGFβ3-mediated palate fusion and TGFβ1-mediated suppression of autoimmunity and generation of Langerhans cells require integrins αvβ6 and αvβ8 but not other RGD-binding integrins as TGFβ activators.
Integrin-linked kinase is required for vitronectin-mediated internalization ofStreptococcus pneumoniaeby host cells
Authors: Bergmann Simone , Lang Anke , Rohde Manfred , Agarwal Vaibhav , Rennemeier Claudia , Grashoff Carsten , Preissner Klaus T. , Hammerschmidt Sven
Published: December 2008

By interacting with components of the human host, including extracellular matrix (ECM) proteins, Streptococcus pneumoniae has evolved various strategies for colonization. Here, we characterized the interaction of pneumococci with the adhesive glycoprotein vitronectin and the contribution of this protein to pneumococcal uptake by host cells in an integrin-dependent manner. Specific interaction of S. pneumoniae with the heparin-binding sites of purified multimeric vitronectin was demonstrated by flow cytometry analysis. Host-cell-bound vitronectin promoted pneumococcal adherence to and invasion into human epithelial and endothelial cells. Pneumococci were trapped by microspike-like structures, which were induced upon contact of pneumococci with host-cell-bound vitronectin. αvβ3 integrin was identified as the major cellular receptor for vitronectin-mediated adherence and uptake of pneumococci. Ingestion of pneumococci by host cells via vitronectin required a dynamic actin cytoskeleton and was dependent on integrin-linked kinase (ILK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), as demonstrated by gene silencing or in inhibition experiments. In conclusion, pneumococci exploit the vitronectin–αvβ3-integrin complex as a cellular receptor for invasion and this integrin-mediated internalization requires the cooperation between the host signalling molecules ILK, PI3K and Akt.
EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility
Authors: Yamazaki Tohru , Masuda Junko , Omori Tsutomu , Usui Ryosuke , Akiyama Hitomi , Maru Yoshiro
Published: December 2008

The Eph-ephrin receptor-ligand system is implicated in cell behavior and morphology. EphA1 is the founding member of the Eph receptors, but little is known about its function. Here, we show that activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner. We also describe a novel interaction between EphA1 and integrin-linked kinase (ILK), a mediator of interactions between integrin and the actin cytoskeleton. The C-terminal sterile α motif (SAM) domain of EphA1 is required and the ankyrin region of ILK is sufficient for the interaction between EphA1 and ILK. The interaction is independent of EphA1 kinase activity but dependent on stimulation of the EphA1 ligand ephrin-A1. Activation of EphA1 kinase resulted in a decrease of ILK activity. Finally, we demonstrated that expression of a kinase-active form of ILK (S343D) rescued the EphA1-mediated spreading defect, and attenuated RhoA activation. These results suggest that EphA1 regulates cell morphology and motility through the ILK-RhoA-ROCK pathway.
Redesign of the Velodrome in Abuja, Job Report
Authors: Stimpfle Bernd
Published: December 2008

The original roof, finalized in 2003 did fail shortly after the installation process during a thunderstorm. The complete membrane was destroyed but the main masts were still in place and not damaged. It was then decided to replace this roof by a more redundant system, but with the same appearance. Main goal for the redesign was to avoid any modification on the main masts, and ideally no replacement of the main suspension cables.

The design was started with the evaluation of different types of large scale cable nets, to achieve a system with a comparable load bearing behaviour. It ended up with a pentagon and hexagon pattern, forming a similar shape like the previous membrane roof, and so with a comparable geometric stiffness.
Simplified Design Tools for Single/Double Curved Membranes and Inflated Cushions
Authors: Wagner Rosemarie
Published: December 2008

Design and manufacturing of membrane structures is closely related to the use of computer programs. Nevertheless it is necessary to have some simple methods describing the load carrying behaviour. These methods are helpful for defining the stresses for the shape of equilibrium before working with computer programs and are necessary to understand the load transfer and are useful tools to check numerical results. In the following the analytical method describing the geometric nonlinear behaviour of cables is transferred to double curved membranes and inflated cushions taking the gas law into account. The analytical results are compared with numerical solutions.
Textile Architecture in the Italian Context
Authors: Campioli Andrea , Mangiarotti Anna , Zanelli Alessandra
Published: December 2008

The paper rediscovers the roots of Italian textile architecture and also previews some results of a national research study, one of whose focuses is the creation of an archive of knowledge for designers, to increase the qualified building of temporary spaces and the practised application of lightweight materials in our context.
Developing Consumer Involvement in Primary Dental Care
Authors: Eaton Kenneth A , Batchelor Paul , Johns David J
Published: December 2008

The seminar on developing consumer involvement in primary dental care, held during the morning of 15th September 2008, was a collaboration between the Lay Advisory Group and Research Committee of the Faculty of General Dental Practice (UK) (FGDP[UK]). As Professor Mike Mulcahy (immediate past Dean of the Faculty) remarked during his address of welcome, it marked a new and exciting development in the Faculty's role in setting and maintaining professional standards for the benefit of patients. It brought together nearly 50 representatives of national bodies, such as the National Audit Office, consumer groups, the Faculty's Lay Advisory Group and Research Committee, the media and others. Many of the national bodies represented at the seminar had published reports on primary dental care during the last five years.
Kids at the Crossroads: Global Childhood and the State
Authors: Hess Julia Meredith , Shandy Dianna
Published: December 2008

The papers here examine the global circulation of both ideologies and practices that underlie the notion of "childhood," as well as the circulation or migration of children themselves. We ask what are the implications of the global circulation of constructions and practices of children and childhood, and how does the state involve itself in these processes? Specifically, the papers look at children and childhood in light of what Bock, Gaskins, and Lancy (2008:4) term "disruptive experiences." Collectively, the papers examine the experiences of Romanian street children in Paris (Terrio), trafficked children in the U.S. (Uehling), the unborn and the recently born children of African asylum seekers in Ireland (Shandy), and the children of Mexican migrants on both sides of the U.S.-Mexico border (Boehm). In these settings children have roles as individual actors, but this agency is tempered by the notion that adult oversight of these youth is frequently a function of the state or a negotiated reality between parents and the state. The articles, social commentary and book reviews therefore provide fodder for recent debates within anthropology that emphasize the role of children as independent actors by highlighting the tension between "structure and agency," and problematizing these terms and their interaction in important ways.
"For My Children:" Constructing Family and Navigating the State in the U.S.-Mexico Transnation
Authors: Boehm Deborah A.
Published: December 2008

Transnational children—ranging from infants to teenagers—reside in, and migrate to and from, both Mexico and the United States. This paper considers this understudied population, the youngest members of Mexican migrant communities, to understand shifting configurations of kinship in a transnational space. By focusing on transnational families with ties to San Luis Potosí and several locales in the U.S. Southwest, I study the everyday experiences of Mexican migrants to demonstrate the presence and power of the U.S. state in family life. This paper examines a dilemma in transnational lives: a primary motivation for migration is to support and benefit children, and yet children are repeatedly in precarious or threatening situations precisely because of transnational movement, their own and that of their family members. The inclusion of children in the study of transnationality, I argue, nuances our understanding of the (re)production and (re)structuring of kinship. Moreover, a focus on children as embedded within families problematizes popular conceptions of migrants as solely autonomous agents, uncovering the multiple ways in which the actions of parents, children, and other family members are repeatedly shaped and constrained by state policies. [Keywords: transnationalism, children, Mexico, transnational children, migrants, migration]
Making the Irish European: Gaelic Honor Politics and Its Continental Contexts*
Authors: Kane Brendan
Published: December 2008

This article looks at Irish attempts to fashion Gaelic elites as members of a European-wide aristocracy. Historiographical consensus holds that a modern Ireland, defined by a confessionalized sense of national consciousness, emerged from the ashes of the Gaelic political system's collapse ca. 1607. Central to that process was the exile experience of Irish nobles in Counter-Reformation Europe. This article reads two Irish texts — Tadhg Ó Cianáin's Imeacht na nIarlaí and Lughaidh Ó Cléirigh's Beatha Aodha Ruaidh Uí Dhomhnaill — to argue that inclusion in a pan-European nobility was not antithetical to traditional Gaelic cultural norms. In doing so, it attempts to soften the contrast between medieval and modern Ireland, to study the relation between provincial elites and central authority in this period of European state formation, and to explore the interplay between new international identities and traditional local authority.
Exercise for Mind and Body: Giulio Mancini, Collecting, and the Beholding of Landscape Painting in the Seventeenth Century*
Authors: Gage Frances
Published: December 2008

This article explores the intellectual foundations for the development of princely art collections, and of Italian picture galleries in particular, as spaces for combined physical and mental exercise and recreation. This study then establishes the relationship between the therapeutic function of picture galleries and the manner in which landscape paintings produced for princely collectors at this moment in Italy embodied ideals of both exercise and repose.
Writing by Caste, Counting the Past: Alphabetic Literacy and Age Consciousness in the Colonial Pátzcuaro Region, 1680-1750
Authors: Althouse Aaron P.
Published: December 2008

In June of 1739, what might have proven to be a festive early-summer afternoon celebrating the fiesta of Corpus Christi in Pátzcuaro (Mexico), instantaneously veered toward deadly combat when a fight broke out in the streets near a commonly used well in the San Augustín neighborhood, close by where the Corpus procession passed. The turn to violence occurred when two groups of men settled an apparently petty dispute with physical measures that ultimately claimed one participant's life. Two Indian nobles, don Juan de Vargas and his nephew, Santiago Valerio, and a Spaniard, Joseph Ruíz (alias Alvarez), composed one party. Two coyotes, Augustín Calvillo and Matías Martínez Serrillo, and a mulatto, Juan Joseph de los Santos, made up the other. The men knew one and other prior to the argument, though it is impossible to glean from the criminal record of the event whether any festering rivalry played into the dispute. Available evidence suggests that Vargas' refusal to accept a sip of charape (a type of pulque) from Ruíz triggered the incident. This rebuff represented an affront that drew Calvillo, Martínez, and Santos into the fray, siding against the native nobles. In the ensuing upheaval, Valerio sustained a fatal stomach wound.
The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease
Authors: Packer Amy N. , Xing Yi , Harper Scott Q. , Jones Lesley , Davidson Beverly L.
Published: December 2008

The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and decreases neuronal gene expression. In this work, we found that levels of several microRNAs (miRNAs) with upstream RE1 sites are decreased in HD patient cortices relative to healthy controls. Interestingly, one of these, the bifunctional brain enriched miR-9/miR-9*, targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates.
Deletion of Mint Proteins Decreases Amyloid Production in Transgenic Mouse Models of Alzheimer's Disease
Authors: Ho Angela , Liu Xinran , Südhof Thomas C.
Published: December 2008

Mints/X11s are neuronal adaptor proteins that bind to amyloid-β precursor protein (APP). Previous studies suggested that Mint/X11 proteins influence APP cleavage and affect production of pathogenic amyloid-β (Aβ) peptides in Alzheimer's disease; however, the biological significance of Mint/X11 binding to APP and their possible role in Aβ production remain unclear. Here, we crossed conditional and constitutive Mint1, Mint2, and Mint3 knock-out mice with transgenic mouse models of Alzheimer's disease overproducing human Aβ peptides. We show that deletion of all three individual Mint proteins delays the age-dependent production of amyloid plaque numbers and Aβ40 and Aβ42 levels with loss of Mint2 having the largest effect. Acute conditional deletion of all three Mints in cultured neurons suppresses the accumulation of APP C-terminal fragments and the secretion of ectodomain APP by decreasing β-cleavage but does not impair subsequent γ-cleavage. These results suggest that the three Mint/X11 proteins regulate Aβ production by a novel mechanism that may have implications for therapeutic approaches to altering APP cleavage in Alzheimer's disease.
Sensory Responses during Sleep in Primate Primary and Secondary Auditory Cortex
Authors: Issa Elias B. , Wang Xiaoqin
Published: December 2008

Most sensory stimuli do not reach conscious perception during sleep. It has been thought that the thalamus prevents the relay of sensory information to cortex during sleep, but the consequences for cortical responses to sensory signals in this physiological state remain unclear. We recorded from two auditory cortical areas downstream of the thalamus in naturally sleeping marmoset monkeys. Single neurons in primary auditory cortex either increased or decreased their responses during sleep compared with wakefulness. In lateral belt, a secondary auditory cortical area, the response modulation was also bidirectional and showed no clear systematic depressive effect of sleep. When averaged across neurons, sound-evoked activity in these two auditory cortical areas was surprisingly well preserved during sleep. Neural responses to acoustic stimulation were present during both slow-wave and rapid-eye movement sleep, were repeatedly observed over multiple sleep cycles, and demonstrated similar discharge patterns to the responses recorded during wakefulness in the same neuron. Our results suggest that the thalamus is not as effective a gate for the flow of sensory information as previously thought. At the cortical stage, a novel pattern of activation/deactivation appears across neurons. Because the neural signal reaches as far as secondary auditory cortex, this leaves open the possibility of altered sensory processing of auditory information during sleep.
Neurogenic and Neuroendocrine Effects of Goldfish Pheromones
Authors: Chung-Davidson Yu-Wen , Rees Christopher Benjamin , Bryan Mara Beth , Li Weiming
Published: December 2008

Goldfish (Carassius auratus) use reproductive hormones as endocrine signals to synchronize sexual behavior with gamete maturation and as exogenous signals (pheromones) to mediate spawning interactions between conspecifics. We examined the differential effects of two hormonal pheromones, prostaglandin F2α(PGF2α) and 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P) on neurogenesis, neurotransmission, and neuronal activities, and on plasma androstenedione (AD) levels. Exposure to waterborne PGF2αinduced a multitude of changes in male goldfish brain. Histological examination indicated an increase in the number of dividing cells in male diencephalon (p< 0.05, Kruskal–Wallis test). Real-time quantitative PCR tests showed elevated levels of transcripts for the salmon gonadotropin-releasing hormone (GnRH) in the male telencephalon and cerebellum (p< 0.005, one-way ANOVA) and for ChAT (choline acetyltransferase) in the male vagal lobe and the brainstem underneath the vagal lobe (p< 0.05, one-way ANOVA). Therefore, PGF2αseemed to modulate male brain plasticity that coincided with behavioral changes during spawning season. Exposure to waterborne 17,20β-P, however, increased circulatory levels of immunoreactive AD in males and the transcripts of androgen receptor and cGnRH-II (chicken-II GnRH) in the female cerebellum (p< 0.05, one-way ANOVA). PGF2αand 17,20β-P thereby seemed to act through distinct pathways to elicit different responses in the neuroendocrine system. This is the first finding that links a specific pheromone molecule (PGF2α) to neurogenesis in a vertebrate animal.
Electrical Coupling of Lobula Plate Tangential Cells to a Heterolateral Motion-Sensitive Neuron in the Fly
Authors: Haag Juergen , Borst Alexander
Published: December 2008

Many motion-sensitive tangential cells of the lobula plate in blowflies are well described with respect to their visual response properties and the connectivity among them. In addition to extensive connections between tangential cells within the lobula plate of one brain hemisphere, there exist many connections between the two hemispheres. Most of these connections have been found for neurons sensitive to horizontal motion. For neurons sensitive to vertical motion, however, only the connection of vertical sensitive cells (VS cells) and a cell (V1 cell) projecting to the other hemisphere has been demonstrated thus far. The ability to identify the presynaptic and postsynaptic cells as well as the good accessibility has made this specific synapse a model for graded transmission of synapses. However, the exact type of synapse, electrical or chemical, is not known. Investigating the connectivity between VS cells 1–3 and the V1 cell by means of dual recordings, we find that the VS cells are coupled via electrical synapses to the V1 cell. The results were confirmed by visualizing dye coupling between VS cells and V1.
Enhanced Adult Neurogenesis and Angiogenesis and Altered Affective Behaviors in Mice Overexpressing Vascular Endothelial Growth Factor 120
Authors: Udo Hiroshi , Yoshida Yuka , Kino Takako , Ohnuki Koichiro , Mizunoya Wataru , Mukuda Takao , Sugiyama Hiroyuki
Published: December 2008

Vascular endothelial growth factor (VEGF) is implicated as a molecular mediator for adult neurogenesis and behavioral effects of antidepressant drugs. However, these potential roles of VEGF in the CNS have not been clarified in model animals. Here we have created transgenic mice overexpressing a short active variant of VEGF-A (VEGF120) in forebrain. Expression of VEGF120 significantly enhanced cell proliferation and angiogenesis, as exemplified by the formation of an enlarged reddish brain. Adult neurogenesis in hippocampus was markedly stimulated without affecting cell differentiation of neural progenitor cells. Hippocampal neurogenesis was particularly robust in young adult animals, but it declined with age and reduced to control levels by 20 weeks under continuous expression of VEGF120. Thus, VEGF alone is not sufficient to support the long-term enhancement of adult neurogenesis, and VEGF-induced vascularization per se does not necessarily predict increased neurogenesis. In transgenic mice, we observed significant changes in affective behaviors. VEGF was found to have not only antidepressant effects but also anxiolytic effects. In addition, we found that VEGF significantly reduced fear and aggression. In contrast, basal activities under natural conditions were not affected much. Unexpectedly, these characteristic behaviors were maintained in older transgenic mice undergoing a reduced level of cell proliferation in hippocampus, suggesting that there is potential dissociation between adult neurogenesis and mood regulation. Our data indicate that VEGF exerts strong neurogenic and angiogenic effects in postnatal brain and influences different forms of affective behaviors.
Cytoplasmic Inclusions of Htt Exon1 Containing an Expanded Polyglutamine Tract Suppress Execution of Apoptosis in Sympathetic Neurons
Authors: King Matthew A. , Goemans Christoph G. , Hafiz Farida , Prehn Jochen H. M. , Wyttenbach Andreas , Tolkovsky Aviva M.
Published: December 2008

Proteins containing extended polyglutamine repeats cause at least nine neurodegenerative disorders, but the mechanisms of disease-related neuronal death remain uncertain. We show that sympathetic neurons containing cytoplasmic inclusions formed by 97 glutamines expressed within human huntingtin exon1–enhanced green fluorescent protein (Q97) undergo a protracted form of nonapoptotic death that is insensitive to Bax deletion or caspase inhibition but is characterized by mitochondrial dysfunction. By treating the neurons with combined cytosine arabinoside and NGF withdrawal, we demonstrate that Q97 confers a powerful resistance to apoptosis at multiple levels: despite normal proapoptotic signaling (elevation of P-ser15–p53 and BimEL), there is no increase of Puma mRNA or Bax activation, both necessary for apoptosis. Even restoration of Bax translocation with overexpressed Puma does not activate apoptosis. We demonstrate that this robust inhibition of apoptosis is caused by Q97-mediated accumulation of Hsp70, which occurs through inhibition of proteasomal activity. Thus, apoptosis is reinstated by short hairpin RNA-mediated knockdown of Hsp70. These findings explain the rarity of apoptotic death in Q97-expressing neurons. Given the proteasomal blockade, we test whether enhancing lysosomal-mediated degradation with rapamycin reduces Q97 accumulation. Rapamycin reduces the amount of nonpathological Q25 by 70% over 3 d, but Q97 accumulation is unaffected. Interestingly, Q47 inclusions form more slowly as a result of constitutive lysosomal degradation, but faster-forming Q97 inclusions escape lysosomal control. Thus, cytoplasmic Q97 inclusions are refractory to clearance by proteasomal and lysosomal systems, leading to a toxicity that dominates over neuroprotective Hsp70. Our findings may explain the rarity of apoptosis but the inevitable cell death associated with polyQ inclusion diseases.
Pharmacology Review
Authors: Greenwood Corryn S. , Colby Christopher E.
Published: December 2008

Advances in the understanding of neonatal pain have created interest in the use of medications during commonly performed procedures in the neonatal intensive care unit. A number of small studies have examined the role of sedatives, narcotics, miscellaneous anesthetics, and neuromuscular blockers in providing a more comfortable experience for the patient during nonemergent tracheal intubation. However, the most effective combination and doses of these medications is currently unknown. This review discusses the findings of selected studies that have been used to improve the intubating experience of patient and clinician.