bluuebunny/crossref_metadata_2025 huggingface dataset:
Bleeding in carriers of hemophilia
Authors: Plug Iris , Mauser-Bunschoten Eveline P. , Bröcker-Vriends Annette H. J. T. , van Amstel Hans Kristian Ploos , van der Bom Johanna G. , van Diemen-Homan Joanna E. M. , Willemse José , Rosendaal Frits R.
Published: March 2006

A wide range of factor VIII and IX levels is observed in heterozygous carriers of hemophilia as well as in noncarriers. In female carriers, extreme lyonization may lead to low clotting factor levels. We studied the effect of heterozygous hemophilia carriership on the occurrence of bleeding symptoms. A postal survey was performed among most of the women who were tested for carriership of hemophilia in the Netherlands before 2001. The questionnaire included items on personal characteristics, characteristics of hemophilia in the affected family members, and carrier testing and history of bleeding problems such as bleeding after tooth extraction, bleeding after tonsillectomy, and other operations. Information on clotting factor levels was obtained from the hospital charts. Logistic regression was used to assess the relation of carrier status and clotting factor levels with the occurrence of hemorrhagic events. In 2004, 766 questionnaires were sent, and 546 women responded (80%). Of these, 274 were carriers of hemophilia A or B. The median clotting factor level of carriers was 0.60 IU/mL (range, 0.05-2.19 IU/mL) compared with 1.02 IU/mL (range, 0.45-3.28 IU/mL) in noncarriers. Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and operations. Carriers of hemophilia bleed more than other women, especially after medical interventions. Our findings suggest that not only clotting factor levels at the extreme of the distribution, resembling mild hemophilia, but also mildly reduced clotting factor levels between 0.41 and 0.60 IU/mL are associated with bleeding. (Blood. 2006;108:52-56)
Mortality rates and causes of death among all HIV-positive individuals with hemophilia in Canada over 21 years of follow-up
Authors: Arnold Donald M. , Julian Jim A. , Walker Irwin R. ,   for the Association of Hemophilia Clinic Directors of Canada
Published: March 2006

Many individuals with hemophilia were infected with human immunodeficiency virus (HIV) in the early 1980s through contaminated blood products. Most also were co-infected with hepatitis C virus (HCV). Deaths among the entire cohort of HIV-positive hemophiliacs in Canada up to 2003 are described. Using registry data, we analyzed Kaplan-Meier survival curves, determined the effect of age at HIV seroconversion on mortality, and described cause-specific proportional mortality patterns over time. Of 2427 Canadians with hemophilia, 660 (27.2%) were HIV-positive, of whom 406 (61.5%) died. In contrast, 114 (6.5%) deaths occurred in HIV-negative controls. Median age at HIV seroconversion was 20 (range, < 1-67 years), and median survival was 15.0 years (95% confidence interval, 13.6-16.4 years). Younger age at HIV seroconversion was associated with improved survival; however, this finding was not explained by differences in causes of death across age groups. Following the introduction of highly active antiretroviral therapy, the proportion of deaths due to acquired immune deficiency syndrome has decreased, while the proportion of deaths due to liver disease has increased. There were 1134 HCV-positive individuals, of whom only 444 (39.2%) were also HIV-positive. Liver disease is a growing health concern among many hemophiliacs, not only those who are HIV-positive.
Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II
Authors: Enders Anselm , Zieger Barbara , Schwarz Klaus , Yoshimi Ayami , Speckmann Carsten , Knoepfle Eva-Maria , Kontny Udo , Müller Christoph , Nurden Alan , Rohr Jan , Henschen Matthias , Pannicke Ulrich , Niemeyer Charlotte , Nurden Paquita , Ehl Stephan
Published: March 2006

Griscelli syndrome (GS) was diagnosed in a 2-year-old patient with oculocutaneous albinism and immunodeficiency, but sequencing of RAB27a revealed only a heterozygous mutation. Due to impaired natural killer (NK) and T-cell cytotoxicity implying a high risk of developing hemophagocytic lymphohistiocytosis (HLH), he was prepared for hematopoietic stem cell transplantation (HSCT). Unexpectedly, a severe bleeding episode occurred that led to the demonstration of disturbed platelet aggregation, reduced plateletdense granules, and impaired platelet degranulation. In combination with neutropenia, this suggested the diagnosis of Hermansky-Pudlak syndrome type II (HPSII) and a novel homozygous mutation in AP3B1 was detected. None of the 3 reported HPSII patients had developed HLH, and our patient seroconverted to Epstein-Barr virus (EBV) without clinical symptoms. HSCT was therefore withheld, and granulocyte-colony-stimulating factor (G-CSF) therapy was initiated and prevented further bacterial infections. At 3 years of age, however, the patient developed, without an obvious trigger, fulminant HLH that was resistant to therapy. This patient shows that careful clinical and molecular diagnosis is essential to differentiate the complex disorders of lysosomal trafficking. HPSII belongs to the group of familial hemophagocytic syndromes and may represent an indication for HSCT. (Blood. 2006;108:81-87)
Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors
Authors: Zhang Meili , Yao Zhengsheng , Zhang Zhuo , Garmestani Kayhan , Goldman Carolyn K. , Ravetch Jeffrey V. , Janik John , Brechbiel Martin W. , Waldmann Thomas A.
Published: March 2006

CD30 is a member of the tumor necrosis factor receptor family. Overexpression of CD30 on some neoplasms versus its limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Anaplastic large-cell lymphoma (ALCL) represents a heterogeneous group of aggressive non-Hodgkin lymphomas characterized by the strong expression of CD30. We investigated the therapeutic efficacy of HeFi-1, a mouse IgG1 monoclonal antibody, which recognizes the ligand-binding site on CD30, and humanized anti-Tac antibody (daclizumab), which recognizes CD25, in a murine model of human ALCL. The ALCL model was established by intravenous injection of karpas299 cells into nonobese diabetic/severe combined immuno-deficient (SCID/NOD) wild-type or SCID/NOD Fc receptor common γ chain–deficient (FcRγ–/–) mice. HeFi-1, given at a dose of 100 μg weekly for 4 weeks, significantly prolonged survival of the ALCL-bearing SCID/NOD wild-type and SCID/NOD FcRγ–/– mice (P < .01) as compared with the control groups. In vitro studies showed that HeFi-1 inhibited the proliferation of karpas299 cells, whereas daclizumab did not inhibit cell proliferation. We demonstrated that the expression of FcRγ on polymorphonuclear leukocytes and monocytes was not required for HeFi-1–mediated tumor growth inhibition in vivo, although it was required for daclizumab.
Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcγRII (CD32), is stable over time and unaffected by cytokines
Authors: van Mirre Edwin , Breunis Willemijn B. , Geissler Judy , Hack C. Erik , de Boer Martin , Roos Dirk , Kuijpers Taco W.
Published: March 2006

We tested the hypothesis that the ratio between the activating and inhibitory Fcγ receptor type II (FcγRII) in neutrophils determines their responsiveness to immune complexes. We measured mRNA levels of FcγRII isoforms and observed differences in the ratio of FcγRIIa to FcγRIIb2 mRNA in granulocytes of 50 white and 10 black healthy volunteers, and found 4 discrete groups of ratios (ie, 4:1; 3:1, 2:1, or 1:1). The response to either dimeric IgG or aggregated IgG (aIgG) was assessed. Up-regulation of CD11b on the surface as well as the elastase release was significantly more pronounced in neutrophils with a high FcγRIIa/FcγRIIb2 mRNA ratio of 4:1 compared with a 2:1 or 1:1 ratio. Individual ratios as well as the functional responsiveness of neutrophils were constant over time, as was tested over 12 months. Neutrophil stimulation with various agents in vitro did not alter the FcγRIIa/FcγRIIb2 mRNA ratio in the neutrophils of these donors, in clear contrast to the findings in their mononuclear cells. We found a strong association between the 2B.4 haplotype of the FCGR2B promoter with increased transcriptional activity in individuals with 1:1 ratios and the more common low-expression 2B.1 haplotype in individuals with FcγRIIa/FcγRIIb2 mRNA ratios of 2:1, 3:1, or 4:1.
Rituximab for steroid-refractory chronic graft-versus-host disease
Authors: Cutler Corey , Miklos David , Kim Haesook T. , Treister Nathaniel , Woo Sook-Bin , Bienfang Don , Klickstein Lloyd B. , Levin Jesse , Miller Katherine , Reynolds Carol , Macdonell Rebecca , Pasek Mildred , Lee Stephanie J. , Ho Vincent , Soiffer Robert , Antin Joseph H. , Ritz Jerome , Alyea Edwin
Published: March 2006

B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome–encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti–B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P < .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome–encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti–B-cell therapy with rituximab may be beneficial for patients with steroidrefractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396.
IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells
Authors: Strengell Mari , Lehtonen Anne , Matikainen Sampsa , Julkunen Ilkka
Published: March 2006

Dendritic cells (DCs) play an important role in innate and adaptive immune responses. In addition to their phagocytic activity, DCs present foreign antigens to naïve T cells and regulate the development of adaptive immune responses. Upon contact with DCs, activated T cells produce large quantities of cytokines such as interferon-γ (IFN-γ) and interleukin (IL)-21, which have important immunoregulatory functions. Here, we have analyzed the effect of IL-21 and IFN-γ on lipopolysaccharide (LPS)-induced maturation and cytokine production of human monocyte-derived DCs. IL-21 and IFN-γ receptor genes were expressed in high levels in immature DCs. Pretreatment of immature DCs with IL-21 inhibited LPS-stimulated DC maturation and expression of CD86 and human leukocyte antigen class II (HLAII). IL-21 pretreatment also dramatically reduced LPS-stimulated production of tumor necrosis factor α, IL-12, CC chemokine ligand 5 (CCL5), and CXC chemokine ligand 10 (CXCL10) but not that of CXCL8. In contrast, IFN-γ had a positive feedback effect on immature DCs, and it enhanced LPS-induced DC maturation and the production of cytokines. IL-21 weakly induced the expression Toll-like receptor 4 (TLR4) and translation initiation region (TIR) domain-containing adaptor protein (TIRAP) genes, whereas the expression of TIR domain-containing adaptor-inducing IFN-β (TRIF), myeloid differentiation (MyD88) 88 factor, or TRIF-related adaptor molecule (TRAM) genes remained unchanged. However, IL-21 strongly stimulated the expression of suppressor of cytokine signaling (SOCS)-1 and SOCS-3 genes. SOCS are known to suppress DC functions and interfere with TLR4 signaling. Our results demonstrate that IL-21, a cytokine produced by activated T cells, can directly inhibit the activation and cytokine production of myeloid DCs, providing a negative feedback loop between DCs and T lymphocytes.
CD31 promotes β1 integrin-dependent engulfment of apoptotic Jurkat T lymphocytes opsonized for phagocytosis by fibronectin
Authors: Vernon-Wilson Elizabeth F , Auradé Frédéric , Brown Simon B
Published: March 2006

Phagocyte integrins, by binding “bridging” molecules, mediate the ingestion of late apoptotic cells and apoptotic bodies by mechanisms that remain obscure. We recently reported that human monocyte-derived macrophages capture viable and apoptotic human leukocytes through homophilic interactions involving CD31 and that CD31 then promotes the engulfment of apoptotic cells or the detachment of viable cells. We now report that CD31 homophilic interactions between phagocyte and target cells lead to activation of phagocyte α5β1 integrin and the engulfment of apoptotic Jurkat T lymphocytes via a fibronectin (Fn) “bridge.” Although Fn and serum served as an opsonin for β1 integrin-dependent phagocytosis of apoptotic leukemic T cells, they failed to do so for neutrophils. Given the complexities and inherent variability of working with primary cells, we have refined our model to show that ligation of CD31 on THP-1 macrophages also regulates β1 integrin-dependent phagocytosis of Fn-coated Latex beads. Thus, selective “tethering” of apoptotic leukocytes by phagocyte CD31 not only discriminates dying from viable cells but also selectively activates phagocyte integrins for the engulfment of apoptotic cells.
Factors associated with adult poisoning in Northern Malaysia: a case-control study
Authors: Fathelrahman A I , Ab Rahman A F , Zain Z Mohd , Tengku M A
Published: March 2006

Data on adult risk factors associated with drug or chemical poisonings in Malaysia are scarce. The objective of the study was to identify possible risk factors associated with adult admissions to the Penang General Hospital (PGH) due to chemical poisoning and/or drug overdose. The present study was a case-control study, conducted over 18 weeks. One hundred acutely poisoned adult patients admitted to PGH during the period from September 2003 to February 2004 were considered as cases. Two hundred patients admitted to the same medical wards for other illnesses, during the same period, were matched for age and gender with the poisoned cases and thus selected as controls. McNemar test and binary logistic were used for univariate analysis and logistic regression analysis for multivariate analyses. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for each predictor variable. Positive histories of psychiatric illness and previous poisoning, problems in boy/girl friend relationships, family problems, marital problems, Indian ethnicity, Chinese ethnicity, living in rented houses and living in a household with less than five people were significant risk factors associated with adult admissions due to poisoning.
Butanol ingestion in an airport hangar
Authors: Bunc M , Pezdir T , Možina H , Možina M , Brvar M
Published: March 2006

1–Butanol is a colourless organic solvent with a rancid sweet odour. 1–Butanol ingestion may result in vomiting, abdominal pain, headache, drowsiness and unconsciousness. We present a 47–year–old male with no previous medical history, who was found comatose and soiled after having vomited while unconscious. On arrival, he had a Glasgow coma scale of 3, tachycardia, hypotension, shallow tachypnoic breathing, hypotonic muscles, absent myotatic reflexes and aromatic odour. The patient was intubated and treated with oxygen, dopamine and volume replacement therapy. Gastric lavage was performed and activated charcoal was given. His initial laboratory test revealed hypokaliemia, renal failure, acidosis with elevated lactate and hypercapnic respiratory insufficiency. Twelve hours after admission, the patient started to respond to a painful stimulus and 4 h later he was conscious. He was extubated 23 h after admission. All pathological laboratory results gradually returned within normal limits. The subsequent toxicological examination of gastric content and urine sample by gas chromatography revealed 1–butanol. On awakening, he confirmed ingestion of a solvent stored in an airport hangar. In conclusion, we describe a patient who ingested an unknown dose of 1–butanol. Symptoms were headache, vomiting, abdominal pain, coma, muscular hypotonus, hypotension, respiratory insufficiency and mixed acidosis. The patient totally recovered after supportive therapy over 30 h. In future cases, intravenous administration of ethanol or even hemodialysis can be considered analogous to the treatment of methanol and ethylene glycol poisoning.
Automated writing evaluation: defining the classroom research agenda
Authors: Warschauer Mark , Ware Paige
Published: March 2006

With the advent of English as a global language, the ability to write well in English across diverse settings and for different audiences has become an imperative in second language education programmes throughout the world. Yet the teaching of second language writing is often hindered by the great amount of time and skill needed to evaluate repeated drafts of student writing. Online Automated Writing Evaluation programmes have been developed as a way to meet this challenge, and the scoring engines driving such programmes have been analysed in a considerable array of psychometric studies. However, relatively little research has been conducted on how AWE is used in the classroom and the results achieved with such use. In this article, we analyse recent developments in automated writing evaluation, explain the bases on which AWE systems operate, synthesize research with these systems, and propose a multifaceted process/product research programme on the instructional use of AWE. We explore this emerging area of inquiry by proposing a range of potential questions, methodologies and analytical tools that can define such a research agenda.
The multiple contexts of online language teaching
Authors: Lund Andreas
Published: March 2006

The purpose of this paper is to describe and discuss some communicative opportunities currently emerging in networked classrooms and their implications for didactics. In particular, I examine multiple contexts that appear and how they give rise to diverse practices. However, such practices often have their origin in out-of-school contexts and not in institutional discourse and curricula. Consequently, we need to understand how these practices can be explored and exploited in educational contexts. Otherwise, schools risk losing out on important cultural change and may fail to prepare learners for emergent communicative opportunities and requirements. In this paper, which is based on a longitudinal study of Norwegian teachers of English practising in technology-rich environments, I discuss the implications of teaching in and across multiple contexts that emerge in technology-rich environments. Findings indicate that we need to develop our notion of didactics so that it supports teachers working across multiple contexts. As such, didactics takes on the characteristics of a boundary object that mediates learning in and across different social worlds.
Computer-mediated cooperative development: non-judgemental discourse in online environments
Authors: Edge Julian
Published: March 2006

Continuing professional development as it is pursued through the interacting paradigms of reflective practice and action research can be facilitated through the disciplined use of non-judgemental discourse. A framework for such purposeful interaction, cooperative development, has been established for face-to-face use among TESOL professionals for some time. It has now been extended into computer-mediated communication via the use of e-mails and instant-messenger. An example of each is analysed, highlighting the continuing importance of affective considerations in both the personal and pedagogic aspects of a teacher’s continuing development.
Regression models for covariance structures in longitudinal studies
Authors: Pan Jianxin , MacKenzie Gilbert
Published: March 2006

A convenient reparametrization of the marginal covariance matrix arising in longitudinal studies is discussed. The new parameters have transparent statistical interpretations, are unconstrained and may be modelled parsimoniously in terms of polynomials of time. We exploit this framework to model the dependence of the covariance structure on baseline covariates, time and their interaction. The rationale is based on the assumption that a homogeneous covariance structure with respect to the covariate space is a testable model choice. Accordingly, we provide methods for testing this assumption by incorporating covariates along with time into the model for the covariance structure. We also present new computational algorithms which can handle unbalanced longitudinal data, thereby extending existing methods. The new model is used to analyse Kenward’s (1987) cattle data, and the findings are compared with published analyses of the same data set.
Bayesian semi-parametric accelerated failure time model for paired doubly interval-censored data
Authors: Komárek Arnošt , Lesaffre Emmanuel
Published: March 2006

In this paper, we propose a methodology which a) evaluates the effect of covariates on doubly interval-censored paired responses, b) is based on minimal parametric assumptions concerning the distributional parts of the model and c) evaluates the association between the two responses of the pair. Our methodology tackles three research questions arising from the Signal Tandmobiel® project, a prospective Flemish (Belgian) longitudinal dental study. The research questions are 1) What is the effect of baseline covariates on the time-to-caries of the permanent right first molars? 2) Is the effect of the covariates the same for the upper and lower teeth? 3) What is the association between the times-to-caries on the upper and lower teeth? Time-to-caries is defined as the difference of two interval-censored observations, caries time and emergence time, and hence it is a doubly interval-censored response. We suggest using an accelerated failure time model with a bivariate smooth error distribution being a mixture of bivariate normal components defined on a fine fixed grid. To deal with the problem of doubly interval censoring, we use Bayesian methodology and Markov chain Monte Carlo sampling.
Charlson Index Is Associated with One‐year Mortality in Emergency Department Patients with Suspected Infection
Authors: Murray Scott B. , Bates David W. , Ngo Long , Ufberg Jacob W. , Shapiro Nathan I.
Published: March 2006

Objectives:
A patient's baseline health status may affect the ability to survive an acute illness. Emergency medicine research requires tools to adjust for confounders such as comorbid illnesses. The Charlson Comorbidity Index has been validated in many settings but not extensively in the emergency department (ED). The purpose of this study was to examine the utility of the Charlson Index as a predictor of one‐year mortality in a population of ED patients with suspected infection.

Methods:
The comorbid illness components of the Charlson Index were prospectively abstracted from the medical records of adult (age older than 18 years) ED patients at risk for infection (indicated by the clinical decision to obtain a blood culture) and weighted. Charlson scores were grouped into four previously established indices: 0 points (none), 1–2 points (low), 3–4 points (moderate), and ≥5 points (high). The primary outcome was one‐year mortality assessed using the National Death Index and medical records. Cox proportional‐hazards ratios were calculated, adjusting for age, gender, and markers of 28‐day in‐hospital mortality.

Results:
Between February 1, 2000, and February 1, 2001, 3,102 unique patients (96% of eligible patients) were enrolled at an urban teaching hospital. Overall one‐year mortality was 22% (667/3,102). Mortality rates increased with increasing Charlson scores: none, 7% (95% confidence interval [CI] = 5.4% to 8.5%); low, 22% (95% CI = 19% to 24%); moderate, 31% (95% CI = 27% to 35%); and high, 40% (95% CI = 36% to 44%). Controlling for age, gender, and factors associated with 28‐day mortality, and using the “none” group as a reference group, the Charlson Index predicted mortality as follows: low, odds ratio of 2.0; moderate, odds ratio of 2.5; and high, odds ratio of 4.7.

Conclusions:
This study suggests that the Charlson Index predicts one‐year mortality among ED patients with suspected infection.
Phospholipase D and the SNARE Sso1p are necessary for vesicle fusion during sporulation in yeast
Authors: Nakanishi Hideki , Morishita Masayo , Schwartz Cindi L. , Coluccio Alison , Engebrecht JoAnne , Neiman Aaron M.
Published: March 2006

Spore formation in Saccharomyces cerevisiae requires the de novo formation of prospore membranes. The coalescence of secretory vesicles into a membrane sheet occurs on the cytoplasmic surface of the spindle pole body. Spo14p, the major yeast phospholipase D, is necessary for prospore membrane formation; however, the specific function of Spo14p in this process has not been elucidated. We report that loss of Spo14p blocks vesicle fusion, leading to the accumulation of prospore membrane precursor vesicles docked on the spindle pole body. A similar phenotype was seen when the t-SNARE Sso1p, or the partially redundant t-SNAREs Sec9p and Spo20p were mutated. Although phosphatidic acid, the product of phospholipase D action, was necessary to recruit Spo20p to the precursor vesicles, independent targeting of Spo20p to the membrane was not sufficient to promote fusion in the absence of SPO14. These results demonstrate a role for phospholipase D in vesicle fusion and suggest that phospholipase D-generated phosphatidic acid plays multiple roles in the fusion process.
A role for the ELAV RNA-binding proteins in neural stem cells: stabilization ofMsi1mRNA
Authors: Ratti Antonia , Fallini Claudia , Cova Lidia , Fantozzi Roberto , Calzarossa Cinzia , Zennaro Eleonora , Pascale Alessia , Quattrone Alessandro , Silani Vincenzo
Published: March 2006

Post-transcriptional regulation exerted by neural-specific RNA-binding proteins plays a pivotal role in the development and maintenance of the nervous system. Neural ELAV proteins are key inducers of neuronal differentiation through the stabilization and/or translational enhancement of target transcripts bearing the AU-rich elements (AREs), whereas Musashi-1 maintains the stem cell proliferation state by acting as a translational repressor. Since the gene encoding Musashi-1 (Msi1) contains a conserved ARE in its 3′ untranslated region, we focused on the possibility of a mechanistic relationship between ELAV proteins and Musashi-1 in cell fate commitment. Colocalization of neural ELAV proteins with Musashi-1 clearly shows that ELAV proteins are expressed at early stages of neural commitment, whereas interaction studies demonstrate that neural ELAV proteins exert an ARE-dependent binding activity on the Msi1 mRNA. This binding activity has functional effects, since the ELAV protein family member HuD is able to stabilize the Msi1 ARE-containing mRNA in a sequence-dependent way in a deadenylation/degradation assay. Furthermore activation of the neural ELAV proteins by phorbol esters in human SH-SY5Y cells is associated with an increase of Musashi-1 protein content in the cytoskeleton. We propose that ELAV RNA-binding proteins exert an important post-transcriptional control on Musashi-1 expression in the transition from proliferation to neural differentiation of stem/progenitor cells.
Protein phosphatase-2A associates with and dephosphorylates keratin 8 after hyposmotic stress in a site- and cell-specific manner
Authors: Tao Guo-Zhong , Toivola Diana M. , Zhou Qin , Strnad Pavel , Xu Baohui , Michie Sara A. , Omary M. Bishr
Published: March 2006

Keratins 8 and 18 (K8 and K18) are regulated by site-specific phosphorylation in response to multiple stresses. We examined the effect and regulation of hyposmotic stress on keratin phosphorylation. K8 phospho-Ser431 (Ser431-P) becomes dephosphorylated in HT29 cells, but hyperphosphorylated on other K8 but not K18 sites in HRT18 and Caco2 cells and in normal human colonic ex vivo cultures. Hyposmosis-induced dephosphorylation involves K8 but not K18, K19 or K20, occurs preferentially in mitotically active cells, and peaks by 6-8 hours then returns to baseline by 12-16 hours. By contrast, hyperosmosis causes K8 Ser431 hyperphosphorylation in all tested cell lines. Hyposmosis-induced dephosphorylation of K8 Ser431-P is inhibited by okadaic acid but not by tautomycin or cyclosporine. The PP2A catalytic subunit co-immunoprecipitated with K8 and K18 after hyposmotic stress in HT29 cells, but not in HRT18 or Caco2 cells where K8 Ser431 becomes hyperphosphorylated. K8 Ser431-P dephosphorylation after hyposmosis was independent of PP2A levels but correlated with increased PP2A activity towards K8 Ser431-P. Therefore, hyposmotic stress alters K8 phosphorylation in a cell-dependent manner, and renders K8 Ser431-P a physiologic substrate for PP2A in HT29 cells as a result of PP2A activation and the physical association with K8 and K18. The divergent hyposmosis versus hyperosmosis K8 Ser431 phosphorylation changes in HT29 cells suggest that there are unique signaling responses to osmotic stress.
Nucleo-cytoplasmic distribution of β-catenin is regulated by retention
Authors: Krieghoff Eva , Behrens Jürgen , Mayr Bernhard
Published: March 2006

β-catenin is the central signalling molecule of the canonical Wnt pathway, where it activates target genes in a complex with LEF/TCF transcription factors in the nucleus. The regulation of β-catenin activity is thought to occur mainly on the level of protein degradation, but it has been suggested that β-catenin nuclear localization and hence its transcriptional activity may additionally be regulated via nuclear import by TCF4 and BCL9 and via nuclear export by APC and axin. Using live-cell microscopy and fluorescence recovery after photobleaching (FRAP), we have directly analysed the impact of these factors on the subcellular localization of β-catenin, its nucleo-cytoplasmic shuttling and its mobility within the nucleus and the cytoplasm. We show that TCF4 and BCL9/Pygopus recruit β-catenin to the nucleus, and APC, axin and axin2 enrich β-catenin in the cytoplasm. Importantly, however, none of these factors accelerates the nucleo-cytoplasmic shuttling of β-catenin, i.e. increases the rate of β-catenin nuclear import or export. Moreover, the cytoplasmic enrichment of β-catenin by APC and axin is not abolished by inhibition of CRM-1-dependent nuclear export. TCF4, APC, axin and axin2 move more slowly than β-catenin in their respective compartment, and concomitantly decrease β-catenin mobility. Together, these data indicate that β-catenin interaction partners mainly regulate β-catenin subcellular localization by retaining it in the compartment in which they are localized, rather than by active transport into or out of the nucleus.
Spatiotemporal dynamics of p21CDKN1A protein recruitment to DNA-damage sites and interaction with proliferating cell nuclear antigen
Authors: Perucca Paola , Cazzalini Ornella , Mortusewicz Oliver , Necchi Daniela , Savio Monica , Nardo Tiziana , Stivala Lucia A. , Leonhardt Heinrich , Cardoso M. Cristina , Prosperi Ennio
Published: March 2006

The cyclin-dependent kinase inhibitor p21CDKN1A plays a fundamental role in the DNA-damage response by inducing cell-cycle arrest, and by inhibiting DNA replication through association with the proliferating cell nuclear antigen (PCNA). However, the role of such an interaction in DNA repair is poorly understood and controversial. Here, we provide evidence that a pool of p21 protein is rapidly recruited to UV-induced DNA-damage sites, where it colocalises with PCNA and PCNA-interacting proteins involved in nucleotide excision repair (NER), such as DNA polymerase δ, XPG and CAF-1. In vivo imaging and confocal fluorescence microscopy analysis of cells coexpressing p21 and PCNA fused to green or red fluorescent protein (p21-GFP, RFP-PCNA), showed a rapid relocation of both proteins at microirradiated nuclear spots, although dynamic measurements suggested that p21-GFP was recruited with slower kinetics. An exogenously expressed p21 mutant protein unable to bind PCNA neither colocalised, nor coimmunoprecipitated with PCNA after UV irradiation. In NER-deficient XP-A fibroblasts, p21 relocation was greatly delayed, concomitantly with that of PCNA. These results indicate that early recruitment of p21 protein to DNA-damage sites is a NER-related process dependent on interaction with PCNA, thus suggesting a direct involvement of p21 in DNA repair.
Stimulation of Gαq-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK
Authors: Street Miyoko , Marsh Stephen J. , Stabach Paul R. , Morrow Jon S. , Brown David A. , Buckley Noel J.
Published: March 2006

Spectrin is a cytoskeletal protein that plays a role in formation of the specialized plasma membrane domains. However, little is known of the molecular mechanism that regulates responses of spectrin to extracellular stimuli, such as activation of G-protein-coupled receptor (GPCR). We have found that αII spectrin is a component of the Gαq/11-associated protein complex in CHO cells stably expressing the M1 muscarinic receptor, and investigated the effect of activation of GPCR on the cellular localization of yellow-fluorescent-protein-tagged αII spectrin. Stimulation of Gαq/11-coupled M1 muscarinic receptor triggered reversible redistribution of αII spectrin following a rise in intracellular Ca2+ concentration. This redistribution, accompanied by non-apoptotic membrane blebbing, required an intact actin cytoskeleton and was dependent on activation of phospholipase C, protein kinase C, and Rho-associated kinase ROCK. Muscarinic-agonist-induced spectrin remodeling appeared particularly active at localized domains, which is clear contrast to that caused by constitutive activation of ROCK and to global rearrangement of the spectrin lattice caused by changes in osmotic pressure. These results suggest a role for spectrin in providing a dynamic and reversible signaling platform to the specific domains of the plasma membrane in response to stimulation of GPCR.
Numerical analysis of the stress intensity factor for two kinds of mixed-mode crack specimens
Authors: Yan X
Published: March 2006

By means of a boundary element method (BEM), this paper is concerned with two kinds of mixed-mode crack specimens, i.e. the three-point bending and shear specimen with an offset edge crack and the ring specimen with a pair of radial cracks under diametral compression. The boundary element method consists of the constant displacement discontinuity element preented by Crouch and starfield and the crack-tip diplacement discontinuity element proposed by the author. Test examples are included to show that the numerical approach is very efficient and accurate for the stress intensity factor calculation of plane elasticity crack problems in both infinite and finite domains. Specifically, the stress intensity factors (SIFs) for these two kinds of mixed-mode crack specimens are given.
Growth analysis of interfacial delamination in a plastic ball grid array package during solder reflow using the global–local finite element model
Authors: Chang K-C , Chiang K-N
Published: March 2006

This work first investigated the initial location of the possible delamination in a plastic ball grid array (PBGA) package under moisture preconditioning and subsequent solder reflow by applying the modified Tsai-Hill failure criteria. The fracture parameters, such as the stress intensity factor (SIF), the strain energy release rate, and the phase angle at the delamination tip, were calculated to study delamination growth. A two-dimensional PBGA finite element model was considered and the hygrothermal stress at the interfaces was calculated to examine the initiation of delamination. A three-dimensional PBGA finite element model was applied in the study of three-dimensional delamination growth. A global-local finite element analysis and two-dimensional linear interfacial fracture mechanics were used to calculate fracture parameters at the delamination tip for different delamination lengths. The effect of vaporized moisture inside the PBGA package on the growing delamination was examined. A series of popcorn experiments on PBGA packages was carried out to verify the simulation results. The agreement between the predicted and experimental results was good.
Deflections, forces, and moments of composite stiffended hypar shell roofs under concentrated load
Authors: Sahoo S , Chakravorty D
Published: March 2006

The present paper applies a combination of an eight-noded shell element with a three-noted beam element, both curved and isoparametric to solve a bending problem of a composite stiffened hypar shell subjected to concentrated load. Benchmark problems are solved to validate the suitability of the approach and a wide variety of stiffened hypar shell problems are solved by varying the boundary condition, lamination, and curvature of the shell. Different depths, arrangements, and eccentricities of stiffeners are considered. Both static deflections and force/moment resultants are examined thoroughly. The performances of the different shell options with varying boundary conditions, stiffener arrangements, and laminations are studied by arranging them rankwise with respect to different shell actions and through a typical relative performance matrix, which will enable a designer to make a rational choice between a number of options.
Adaptive neural network model based predictive control of an internal combustion engine with a new optimization algorithm
Authors: Wang S W , Yu D L , Gomm J B , Page G F , Douglas S S
Published: March 2006

This paper presents an application of adaptive neural network modelling and model-based predictive control (MPC) for an engine simulation. A radial basis function (RBF) neural network trained by a recursive least-squares (RLS) algorithm is compared with the network with fixed parameters and demonstrated to be more suitable for modelling the crankshaft speed, the intake manifold pressure, and the manifold temperature. Based on the obtained adaptive neural network model, an MPC strategy for controlling the crankshaft speed is realized successfully. A reduced Hessian method, a newly developed sequential quadratic programming (SQP) method for solving non-linear programming (NLP) problems, is implemented to solve the non-linear optimization in MPC. Some important modifications are proposed for the algorithm settings in this research to make the reduced Hessian method more appropriate for the adaptive neural network model based predictive control strategy of internal combustion (IC) engines.
Intake system design procedure for engines with special requirements
Authors: Pogorevc P , Kegl B
Published: March 2006

Intake manifolds provide fresh air to internal combustion engines and have a major effect on their performance. Therefore, many investigations are related to their design in order to improve the charging efficiency and to achieve the uniform distribution of fresh air among the engine cylinders. This paper deals with the design procedure of a cheap multipoint injection intake system, adapted to a racing car engine. Some special demands had to be taken into consideration. The intake manifold must contain the imposed constraint for the airflow in the shape of a single circular restrictor placed between the throttle and the engine to limit its power. The flow and the pressure loss reduction in the engine intake region were investigated with computational fluid dynamics software. Two different geometries of the intake manifold were taken into consideration. On the basis of the numerically obtained three-dimensional results, a mathematical model of the engine with a more appropriate intake was made in the engine simulation code in order to anticipate its characteristics. The intake system was designed, practically manufactured, and tested in the laboratory. The experimental results confirmed numerical predictions, justifying the simple and relatively quick design procedure for the intake system.
Nanotube multi-functional nanoposition sensors
Authors: Liu P , Dong L , Arai F , Fukuda T
Published: March 2006

Prototypes of indvidual carbon-nanotube-based nanoposition sensors for detercting approaching, touching, and sliding positions are presented on the bases of the interelectrodedistance-based field emission current change of a nanotube emitterand the resistance change caused by sliding motion of nanotube on an Au substrate. The sensors are constroucted by nanorobotic manipulation and featured by their compact sizes, simple structures, and potential high resolutions. A field-emission-based sensor is characterized by the non-contact configuration and is suitable for approximity sensing or as a position detector for other kinds of sensor. The perfect linearity of the resistance of a nanotube sliding on an Au substrate promises very high resolution for distance measurement. The sensitivity of these sensors has been found to be 7pA per 100nm and 0.24nA/nm respectively in experiments. The transient state from emission to transpot can be used for a touching sensor, and a 52 pA jump has been detected.
Improving organic/electrode interface in organic light-emitting diodes by soft contact Iamination
Authors: Lee T-W , Hsu J. W. P.
Published: March 2006

Organic light-emitting diodes (OLEDs), with few exvceptions, are fabricated in the standard way of sequentially depositing active layers and elecrodes onto a substrate. The conventional devices have ‘a detrimental layer’ at the interface between the organic and the top metal electrode because evaporation results in metal in-diffusion and chemical disruption at the metal-organic interface, Here, a different approach is introduced to construct OLEDs: soft contact lamination (SCL) is based on thysical lamination of thin metal electrodes supported by an elastomeric layer against the electrolumnescent organic layer. Thei method produces spatially homogeneous, intimate contacts via van der Waals interaction between the metal and the organic, resulting in no chemical and physical damages to the organic. Devices fabricated by SCL are shown to have no detrimental layer and fewer luminescence-quenching channels than conventional devices that have evaporated top metal electrodes.
Prototype detector technology for the SCUBA-2 submillimetre bolometer array
Authors: Walton A. J. , Parkes W , Terry J. G. , Dunare C , Stevenson J. T. M. , Gundlach A. M. , Bunting A , Smith S , Hilton G. C. , Irwin K. D. , Ullom J. N. , Duncan W. D. , Holland W. S. , Audley M. D. , McGregor H , Ade P. A. R. , Sudiwala R. V. , Woodcraft A. L. , Schulte E
Published: March 2006

This paper reports the latest design and the associated fabrication technology of the Mk II prototype infrared (IR) detector for the two 5120 pixel SCUBA-2 (submillimetre common user bolometer arry) instruments, which are to be mounted on the James Clerk Maxwell telescope (JCMT) in Hawaii. Progress is described on the design and the technology modules being developed for the new detector, which is based upon silicon micromachining. The two arrays of transition edge sensors (TES) are used to detect incoming radiation with wavelengths of 450 and 850 μ respectively and as the SCUBA-2 detector operates at about 100 mK, it consequently involves integration with low-temperature electronics and careful design of the associated interconnect. A key aspect of the connection between the TES detector and readout electronics is the use of indium flip-chip bumps, which become superconducting at cryogenic temperatures. The integration of nanoscale membranes and transition edge sensors together with microsystem technology enables SCUBA-2 to have of the order of 10 -17W (1 Hz bandwidth) sensitivity to incoming radiation.
Preparation of Poly(3,4-dibutoxy-2,5-thienylene-vinylene) via Titanium-Induced Dicarbonyl-Coupling Reaction of 3,4-Dibutoxythiophene-2,5-dicarbaldehyde
Authors: Iwatsuki Shouji , Kubo Masataka , Itoh Yoshiaki
Published: March 2006

3,4-Dibutoxythiophene-2,5-dicarbaldehyde was found to be readily subject to the titanium-induced dicarbonyl-coupling reaction to give poly(3,4-dibutoxy-2,5-thienylene-vinylene) with molecular weight of 35000 and high solubility in organic solvent like chloroform. In addition electroconductivity and third-order nonlinear optical susceptibility for its polymer film were measured.
Addition-Fragmentation Chain Transfer in Free Radical Styrene Polymerization in the Presence of 2,4-Diphenyl-4-methyl-1-pentene
Authors: Watanabe Yasumasa , Ishigaki Hideyo , Okada Hiroshi , Suyama Shuji
Published: March 2006

Thermal polymerization of styrene in the presence of 2,4-diphenyl-4-methyl-1-pentene (α-MSD) gave a low molecular weight polymer having a terminal double bond and a cumyl moiety without lowering the polymerization rate. A chain transfer mechanism through addition-fragmentation reaction is presented.
Regioselective Mono-2-C-iodination of Fully Methylated Cyclodextrins through Interconversions between Cyclic and Acyclic Structures
Authors: Sakairi Nobuo , Kuzuhara Hiroyoshi
Published: March 2006

An efficient procedure for modification at C-2 position of fully methylated α-, β-, and γ-cyclodextrins was achieved by thiolytic fission of one of their glycosidic bonds, followed by conversion of the resulting 1-thioglycosides into glycals and addition of iodonium ion accompanied intramolecular glycosidation, giving novel methylated cyclooligosaccharides containing 2-deoxy-2-iodo-α-d-mannopyranosyl moiety as one of the constituents.
Inhomogeneous Aggregation of a Merocyanine Dye at the Solid/Liquid Interface Layer. A Picosecond Time-Resolved Total Internal Reflection Fluorescence Study
Authors: Hamai Sanyo , Tamai Naoto , Masuhara Hiroshi
Published: March 2006

Fluorescence spectra and their rise and decay dynamics of a merocyanine dye in the interface layer have been studied as a function of penetration depth of the evanescent wave intensity by total internal reflection fluorescence spectroscopy. The aggregation of the dye was enhanced in the interface layer of up to ≈ 100 nm thickness compared to the bulk solution.
Molecular Resolution Image of Lignoceric Acid Monolayer with Atomic Force Microscope
Authors: Kajiyama Tisato , Oishi Yushi , Hirose Fuminobu , Shuto Kenshiro , Kuri Taishi
Published: March 2006

A molecular resolution image of lignoceric acid monolayer, which was prepared on the water surface at a subphase temperature of 293 K and transferred onto a mica substrate, was successfully observed with an atomic force microscope(AFM) for the first time. The AFM image of the monolayer showed two-dimensional regular array with locally disordered molecular arrangements.
Silica-Containing Mixed-Oxide Gels Prepared by a Coprecipitation Method as Novel Packing Materials for Liquid Chromatography
Authors: Kaneko Shoji , Mitsuzawa Tadatoshi , Ohmori Satoshi , Nakamura Motoshi , Nobuhara Kazunori , Masatani Mitsuhiro
Published: March 2006

The separation characteristics of silica-zirconia. silica-alumina, Silica-titania, and silica-magnesia gels for benzene, dimethyl phthalate, and pyridine have been evaluated as column packing materials for liquid chromatography. Of these mixed-oxide gels, silica-magnesia had the best separation ability particularly for a basic compound, pyridine depending presumably on the reduction of the activity of silanol group on silica surface.
Preparation of a Self-Supporting, Multilayered Film of Montmorillonite
Authors: Isayama Munetoshi , Sakata Kanji , Kunitake Toyoki
Published: March 2006

A self-supporting, multilayered film which was prepared from an aqueous dispersion of montmorillonite and orthophosphoric acid (H3PO4) remained intact even in hot water and maintained the ion exchange capacity similar to that of the original montmorillonite powder. An ammonium surfactant (CTAB) was intercalated into this film readily to give a highly oriented composite film.