bluuebunny/crossref_metadata_2025 huggingface dataset:
The small 11kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells
Authors: Chen Aaron Yun , Zhang Elizabeth Yan , Guan Wuxiang , Cheng Fang , Kleiboeker Steve , Yankee Thomas M. , Qiu Jianming
Published: October 2009

Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5kDa, 11kDa, and NS1, for their function in inducing apoptosis in transfection of primary ex vivo–expanded erythroid progenitor cells, in comparison with apoptosis induced during B19V infection. Our results show that 11kDa is a more significant inducer of apoptosis than NS1, whereas 7.5kDa does not induce apoptosis. Furthermore, we determined that caspase-10, an initiator caspase in death receptor signaling, is the most active caspase in apoptotic erythroid progenitors induced by 11kDa and NS1 as well as during B19V infection. More importantly, cytoplasm-localized 11kDa is expressed at least 100 times more than nucleus-localized NS1 at the protein level in primary erythroid progenitor cells infected with B19V; and inhibition of 11kDa expression using antisense oligos targeting specifically to the 11kDa-encoding mRNAs reduces apoptosis significantly during B19V infection of erythroid progenitor cells. Taken together, these results demonstrate that the 11kDa protein contributes to erythroid progenitor cell death during B19V infection.
Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome
Authors: Moore Iain , Strain Lisa , Pappworth Isabel , Kavanagh David , Barlow Paul N. , Herbert Andrew P. , Schmidt Christoph Q. , Staniforth Scott J. , Holmes Lucy V. , Ward Roy , Morgan Lynn , Goodship Timothy H. J. , Marchbank Kevin J.
Published: October 2009

Factor H autoantibodies have been reported in approximately 10% of patients with atypical hemolytic uremic syndrome (aHUS) and are associated with deficiency of factor H–related proteins 1 and 3. In this study we examined the prevalence of factor H autoantibodies in the Newcastle cohort of aHUS patients, determined whether the presence of such autoantibodies is always associated with deficiency of factor H–related proteins 1 and 3, and examined whether such patients have additional susceptibility factors and/or mutations in the genes encoding complement regulator/activators. We screened 142 patients with aHUS and found factor H autoantibodies in 13 individuals (age 1-11 years). The presence of the autoantibodies was confirmed by Western blotting. By using multiplex ligation-dependent probe amplification we measured complement factor H–related (CFHR)1 and CFHR3 copy number. In 10 of the 13 patients there were 0 copies of CFHR1, and in 3 patients there were 2. In 3 of the patients with 0 copies of CFHR1 there was 1 copy of CFHR3, and these individuals exhibited a novel deletion incorporating CFHR1 and CFHR4. In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1 in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent factors may be necessary in individual patients for disease manifestation.
Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia
Authors: Nakahara Fumio , Sakata-Yanagimoto Mamiko , Komeno Yukiko , Kato Naoko , Uchida Tomoyuki , Haraguchi Kyoko , Kumano Keiki , Harada Yuka , Harada Hironori , Kitaura Jiro , Ogawa Seishi , Kurokawa Mineo , Kitamura Toshio , Chiba Shigeru
Published: October 2009

Hairy enhancer of split 1 (Hes1) is a basic helix-loop-helix transcriptional repressor that affects differentiation and often helps maintain cells in an immature state in various tissues. Here we show that retroviral expression of Hes1 immortalizes common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) in the presence of interleukin-3, conferring permanent replating capability on these cells. Whereas these cells did not develop myeloproliferative neoplasms when intravenously administered to irradiated mice, the combination of Hes1 and BCR-ABL in CMPs and GMPs caused acute leukemia resembling blast crisis of chronic myelogenous leukemia (CML), resulting in rapid death of the recipient mice. On the other hand, BCR-ABL alone caused CML-like disease when expressed in c-Kit-positive, Sca-1-positive, and lineage-negative hematopoietic stem cells (KSLs), but not committed progenitors CMPs or GMPs, as previously reported. Leukemic cells derived from Hes1 and BCR-ABL-expressing CMPs and GMPs were more immature than those derived from BCR-ABL-expressing KSLs. Intriguingly, Hes1 was highly expressed in 8 of 20 patients with CML in blast crisis, but not in the chronic phase, and dominant negative Hes1 retarded the growth of some CML cell lines expressing Hes1. These results suggest that Hes1 is a key molecule in blast crisis transition in CML.
Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms
Authors: Duckers Connie , Simioni Paolo , Spiezia Luca , Radu Claudia , Dabrilli Paolo , Gavasso Sabrina , Rosing Jan , Castoldi Elisabetta
Published: October 2009

Coagulation factor V (FV), present in plasma and platelets, is indispensable to thrombin formation, yet patients with undetectable plasma FV seldom experience major bleeding. We used thrombin generation assays to explore the role of platelet FV in 4 patients with severe congenital FV deficiency (3 with plasma FV clotting activity [FV:C] < 1%). When triggered with tissue factor (TF) concentrations up to 50pM, platelet-poor plasma (PPP) from the patients with undetectable plasma FV showed no thrombin generation, whereas platelet-rich plasma (PRP) formed thrombin already at 1 to 5pM of TF. Thrombin generation in PRP from the FV-deficient patients was enhanced to near-normal levels by platelet activators (collagen or Ca2+-ionophore) and could be completely suppressed by specific FV inhibitors, suggesting FV dependence. Accordingly, platelet FV antigen and activity were measurable in all FV-deficient patients and platelet FVa could be visualized by Western blotting. Normalization of the tissue factor pathway inhibitor (TFPI) level, which is physiologically low in FV-deficient plasma, almost completely abolished thrombin generation in PRP from the FV-deficient patients. In conclusion, patients with undetectable plasma FV may contain functional FV in their platelets. In combination with low TFPI level, residual platelet FV allows sufficient thrombin generation to rescue these patients from fatal bleeding.
High resolution analysis of the human transcriptome: detection of extensive alternative splicing independent of transcriptional activity
Authors: Zhou Weiyin , Calciano Margaret A , Jordan Heather , Brenner Michael , Johnson Seth , Wu Darong , Lei Lin , Pallares Diego , Beurdeley Pascale , Rouet Fabien , Gill Pritmohinder S , Bracco Laurent , Soucaille Cyril , Einstein Richard
Published: October 2009

Background

Commercially available microarrays have been used in many settings to generate expression profiles for a variety of applications, including target selection for disease detection, classification, profiling for pharmacogenomic response to therapeutics, and potential disease staging. However, many commercially available microarray platforms fail to capture transcript diversity produced by alternative splicing, a major mechanism for driving proteomic diversity through transcript heterogeneity.

Results

The human Genome-Wide SpliceArray™ (GWSA), a novel microarray platform, utilizes an existing probe design concept to monitor such transcript diversity on a genome scale. The human GWSA allows the detection of alternatively spliced events within the human genome through the use of exon body and exon junction probes to provide a direct measure of each transcript, through simple calculations derived from expression data. This report focuses on the performance and validation of the array when measured against standards recently published by the Microarray Quality Control (MAQC) Project. The array was shown to be highly quantitative, and displayed greater than 85% correlation with the HG-U133 Plus 2.0 array at the gene level while providing more extensive coverage of each gene. Almost 60% of splice events among genes demonstrating differential expression of greater than 3 fold also contained extensive splicing alterations. Importantly, almost 10% of splice events within the gene set displaying constant overall expression values had evidence of transcript diversity. Two examples illustrate the types of events identified: LIM domain 7 showed no differential expression at the gene level, but demonstrated deregulation of an exon skip event, while erythrocyte membrane protein band 4.1 -like 3 was differentially expressed and also displayed deregulation of a skipped exon isoform.

Conclusion

Significant changes were detected independent of transcriptional activity, indicating that the controls for transcript generation and transcription are distinct, and require novel tools in order to detect changes in specific transcript quantity. Our results demonstrate that the SpliceArray™ design will provide researchers with a robust platform to detect and quantify specific changes not only in overall gene expression, but also at the individual transcript level.
Comparative study of enteric viruses, coliphages and indicator bacteria for evaluating water quality in a tropical high-altitude system
Authors: Espinosa Ana C , Arias Carlos F , Sánchez-Colón Salvador , Mazari-Hiriart Marisa
Published: October 2009

Background

Bacteria used as indicators for pathogenic microorganisms in water are not considered adequate as enteric virus indicators. Surface water from a tropical high-altitude system located in Mexico City that receives rainwater, treated and non-treated wastewater used for irrigation, and groundwater used for drinking, was studied.

Methods

The presence of enterovirus, rotavirus, astrovirus, coliphage, coliform bacteria, and enterococci was determined during annual cycles in 2001 and 2002. Enteric viruses in concentrated water samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Coliphages were detected using the double agar layer method. Bacteria analyses of the water samples were carried out by membrane filtration.

Results

The presence of viruses and bacteria in the water used for irrigation showed no relationship between current bacterial indicator detection and viral presence. Coliphages showed strong association with indicator bacteria and enterovirus, but weak association with other enteric viruses. Enterovirus and rotavirus showed significant seasonal differences in water used for irrigation, although this was not clear for astrovirus.

Conclusion

Coliphages proved to be adequate faecal pollution indicators for the irrigation water studied. Viral presence in this tropical high-altitude system showed a similar trend to data previously reported for temperate zones.
Developing capacity in health informatics in a resource poor setting: lessons from Peru
Authors: Kimball Ann Marie , Curioso Walter H , Arima Yuzo , Fuller Sherrilynne , Garcia Patricia J , Segovia-Juarez Jose , Castagnetto Jesus M , Leon-Velarde Fabiola , Holmes King K
Published: October 2009

The public sectors of developing countries require strengthened capacity in health informatics. In Peru, where formal university graduate degrees in biomedical and health informatics were lacking until recently, the AMAUTA Global Informatics Research and Training Program has provided research and training for health professionals in the region since 1999. The Fogarty International Center supports the program as a collaborative partnership between Universidad Peruana Cayetano Heredia in Peru and the University of Washington in the United States of America. The program aims to train core professionals in health informatics and to strengthen the health information resource capabilities and accessibility in Peru. The program has achieved considerable success in the development and institutionalization of informatics research and training programs in Peru. Projects supported by this program are leading to the development of sustainable training opportunities for informatics and eight of ten Peruvian fellows trained at the University of Washington are now developing informatics programs and an information infrastructure in Peru. In 2007, Universidad Peruana Cayetano Heredia started offering the first graduate diploma program in biomedical informatics in Peru.
Genetic and pharmacological inhibition of calcineurin corrects the BDNF transport defect in Huntington's disease
Authors: Pineda Jose R , Pardo Raúl , Zala Diana , Yu Hua , Humbert Sandrine , Saudou Frédéric
Published: October 2009

Background

Huntington's disease (HD) is an inherited neurogenerative disease caused by an abnormal expansion of glutamine repeats in the huntingtin protein. There is currently no treatment to prevent the neurodegeneration caused by this devastating disorder. Huntingtin has been shown to be a positive regulator of vesicular transport, particularly for neurotrophins such as brain-derived neurotrophic factor (BDNF). This function is lost in patients with HD, resulting in a decrease in neurotrophic support and subsequent neuronal death. One promising line of treatment is therefore the restoration of huntingtin function in BDNF transport.

Results

The phosphorylation of huntingtin at serine 421 (S421) restores its function in axonal transport. We therefore investigated whether inhibition of calcineurin, thebona fidehuntingtin S421 phosphatase, restored the transport defects observed in HD. We found that pharmacological inhibition of calcineurin by FK506 led to sustained phosphorylation of mutant huntingtin at S421. FK506 restored BDNF transport in two complementary models: rat primary neuronal cultures expressing mutant huntingtin and mouse cortical neurons fromHdhQ111/Q111HD knock-in mice. This effect was the result of specific calcineurin inhibition, as calcineurin silencing restored both anterograde and retrograde transport in neurons fromHdhQ111/Q111mice. We also observed a specific increase in calcineurin activity in the brain ofHdhQ111/Q111mice potentially accounting for the selective loss of huntingtin phosphorylation and contributing to neuronal cell death in HD.

Conclusion

Our results validate calcineurin as a target for the treatment of HD and provide the first demonstration of the restoration of huntingtin function by an FDA-approved compound.
Glucose Promotes the Production of Interleukine-1β and Cyclooxygenase-2 in Mesangial Cells via Enhanced (Pro)Renin Receptor Expression
Authors: Huang Jiqian , Siragy Helmy M.
Published: October 2009

(Pro)renin receptor (PRR) is present in renal glomeruli, and its expression is up-regulated in diabetes. Similarly, renal inflammation is increased in the presence of hyperglycemia. The linkage between PRR and renal inflammation is not well established. We hypothesized that glucose-induced up-regulation of PRR leads to increased production of the proinflammatory factors IL-1β and cyclooxygenase-2 (COX-2). Studies were conducted in rat mesangial cells (RMCs) exposed to 30 mmd-glucose for 2 wk followed by PRR small interfering RNA knockdown, IL-1 receptor blockade with IL-1 receptor antagonist or angiotensin II type 1 receptor blockade with valsartan. The results showed that d-glucose treatment up-regulates prorenin, renin, angiotensin II, PRR, IL-1β, and COX-2 mRNA and protein expression and increases phosphorylation of ERK1/2, c-Jun N-terminal kinase, c-Jun, and nuclear factor-κB (NF-κB) p65 (serine 276,468 and 536), respectively. PRR small interfering RNA attenuated PRR, IL-1β, and COX-2 mRNA and protein expressions and significantly decreased angiotensin II production and phosphorylation of ERK1/2 and NF-κB p65 associated with high glucose exposure. Similarly, IL-1 receptor antagonist significantly reduced COX-2 mRNA and protein expression induced by high glucose. COX-2 inhibition reduced high-glucose-induced PRR expression. We conclude that glucose induces the up-regulation of PRR and its ligands prorenin and renin, leading to increased IL-1β and COX-2 production via the angiotensin II-dependent pathway. It is also possible that PRR could enhance the production of these inflammatory cytokines through direct stimulation of ERK1/2-NF-κB signaling cascade.
“No Abstract Art Here”: The Problem of the Visual in Contemporary Anglo-Caribbean Art
Authors: Thompson Krista A.
Published: October 2009

Some critics contend that the visual language of abstraction or conceptual art cannot translate “Caribbeanness.” This essay considers the work of several contemporary Caribbean artists who highlight how the “picturesque” paintings so favored by detractors were historically constructed to erase the multiple realities and visual imaginaries of the islands.
From Mythologies to Realities: The Iconography of Ras Daniel Heartman
Authors: Ama
Published: October 2009

Few Jamaican visual artists have been able to capture the quintessence of Jamaican identity in the way that Ras Daniel Heartman did, exposing powerful images of Rastafari that are unequalled in any genre. While reggae music provided a soundtrack to the conscious struggle for self-determination, Ras Daniel's work parallels that aesthetic in the visual arts.
Danger and Desire: Crossings are Never Undertaken All at Once or Once and for All
Authors: Alexander M. Jacqui
Published: October 2009

This essay stages a meeting among the authors of the three reflections on Pedagogies of Crossings. Using danger and desire as the tropes of entry, it returns to Pedagogies by way of wrestling with their most salient preoccupations: the need for a visible pedagogy of the erotic; the importance of bringing sex to our engagement of the erotic and to our experience of the Sacred; and the urgency of addressing the analytic and political fissures between Caribbean feminists at home and those abroad. It ends by underscoring the need for a collective politics that re-imagines our deep yearnings to live sovereign lives.
Virtual Islands: Mobilities, Connectivity, and the New Caribbean Spatialities
Authors: Sheller Mimi
Published: October 2009

Many parts of the Caribbean region are being respatialized, rescaled and reterritorialized through processes of neoliberal development, intraregional and international mobility, and complex spatial restructuring of physical infrastructures and virtual realities. Drawing on the sociology of mobilities and space, this article suggests that changes in technologies of transportation and communciation, media discourses, and cultural performances of travel within recent regimes of neoliberal governance and regulation are contributing to new ways of developing, curating and staging neocolonial fantasies of the untouched Caribbean paradise.
The Fact of Blackness? The Bleached Body in Contemporary Jamaica
Authors: Brown-Glaude Winnifred
Published: October 2009

This essay examines public discussions around skin bleaching in Jamaica and demonstrates that a discourse of pathology is a dominant frame of meaning used to explain this practice. I argue that the practice of bleaching destabilizes popular conceptions of blackness that rely on an understanding of the body as immutable and naturally marked by race. Depicting skin bleaching as pathological attempts to recenter hegemonic conceptions of blackness and to discipline bodies so that they adhere to them.
Gendered Legacies of Romantic Nationalism in the Works of Michelle Cliff
Authors: Stitt Jocelyn Fenton
Published: October 2009

This essay argues that Jamaican-American Michelle Cliff's writing should be understood within a new interpretive framework which sees post-independence Caribbean literature as inheriting gendered and raced legacies of Romantic nationalism. While Cliff's early work shows the appeal of Romantic nationalism as a means of establishing national authenticity, her later work demonstrates how these norms, when transmitted to postcolonial black nationalism, displace more complex notions of national identity that take into account racial, sexual, and cultural hybridity.
Intuitive Art as a Canon
Authors: Poupeye Veerle
Published: October 2009

This paper examines the Intuitives concept and the controversies that have surrounded this artistic genre in Jamaica. It argues that Intuitive art, as it has been defined by the National Gallery of Jamaica, constitutes a specialized canon within the national canons, rather than an alternative to Primitive or Naïve. While its reliance on notions of purity and autonomy are unwittingly Primitivist, the concept has given legitimacy to the artists and allowed them to produce work that would otherwise never have existed.
Caribbean Subjectivity and the Colonial Archive
Authors: Tobin Beth Fowkes
Published: October 2009

This essay takes up a question that Krista Thompson poses in An Eye for the Tropics about whether the highly tropicalized and touristic imagery found in colonial photographs can be used to narrate black histories. She asks: “Can postcards, the very representations that denied historicity to the black population, ever unproblematically yield `black history'? Can black histories ever be built on fragile postcard infrastructures?”
Fracturing Subjectivities: International Space and the Discourse of Individualism in Colin Channer's Waiting in Vain and Jamaica Kincaid's Mr. Potter
Authors: Forbes Curdella
Published: October 2009

This article addresses a concept of individualism that has emerged in some contemporary Caribbean fictions. I examine the evidence of this in a general way and then with reference to Jamaica Kincaid's Mr. Potter and Colin Channer's Waiting in Vain. I suggest that their individualism, though seemingly anomalous to diasporan thought, is in fact an “uncanny” product of the diasporan search for connections across borders.
“Call the Police. Call the Army. Call God. And Let's Have One Helluva Big Story”: On Writing Caribbean Art Histories After Postcoloniality
Authors: Thompson Krista A.
Published: October 2009

Are there intrinsic and unique ways of representing the “visual atmospherics” of the Caribbean? Might phenomenological studies of embodied perception offer insight into distinct forms of Caribbean visuality? How would contrapuntal interpretations of colonial archives result in a decolonizing art history? What are the larger stakes of these ways of reading Caribbean visual cultures, and what might they leave unseen? This article points to the need to radically interrogate and historically situate the object of art historical study in the region.
Diasporic Disciplining of Caliban? Haiti, the Dominican Republic, and Intra-Caribbean Politics
Authors: Braziel Jana Evans
Published: October 2009

In her contribution, Braziel resists Torres-Saillant's valorization of diaspora as the anti-dote to national paradigms. As an organizing rubric, “Caribbean diaspora” obscures nationality, class, race, gender, sexuality, and political economy as striating diasporas and diasporic communities; it ignores the fact that there is not one Caribbean diaspora but many. Diasporas are fractured landscapes: not only oppressed individuals but also corrupt presidents and even petty but violent Calibans are part of out-migratory waves that constitute diasporic formations abroad, or form the long-arm, transnational tentacles of the nation-state.
On the Impossibility of All Possibility in Caribbean Theory
Authors: Buscaglia-Salgado José F.
Published: October 2009

Silvio Torres-Saillant's passionate defense of Caribbean intellectual traditions is far from being “an intellectual history of the Caribbean.” Nevertheless, this is an indispensable book, both for what it says and for the Antillean passion that drives the author's argument, as well as for its silences, errors, and innumerable paths of deviation and reflection that it opens. The work is a truly Caribbean contraption, combining autobiography, philosophical argumentation, certain features of the political manifesto, and various modalities of criticism with a good deal of historical narrative and discursive inventiveness.
Black Memory versus State Memory: Notes toward a Method
Authors: Hanchard Michael
Published: October 2009

In addition to providing some conceptual and theoretical cues from fiction, literary and visual criticism, history, and philosophy that treat the subject of memory, this paper provides an outline of a critical method to distinguish among various deployments of black memory. This paper highlights and explores some of the tensions between state and popular memory in the discourses of transnational black politics, as well as in the development and circulation of state sanctioned national history within national societies.
The Founding Myths of the Haitian Nation
Authors: Laroche Maximilien
Published: October 2009

Translated by Martin Munro.
Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains
Authors: Aoyama Takane , Hata Suguru , Nakao Takeshi , Tanigawa Yuka , Oka Chio , Kawaichi Masashi
Published: October 2009

Deficiency of caytaxin results in hereditary ataxia or dystonia in humans, mice and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as caytaxin-binding proteins. The tetratricopeptide-repeat region of KLC1 recognizes the ELEWED sequence (amino acids 115-120) of caytaxin. This motif is conserved among BNIP-2 family members and other KLC-interacting kinesin cargo proteins such as calsyntenins. Caytaxin associates with kinesin heavy chains (KHCs) indirectly by binding to KLCs, suggesting that caytaxin binds to the tetrameric kinesin molecule. In cultured hippocampal neurons, we found that caytaxin is distributed in both axons and dendrites in punctate patterns, and it colocalizes with microtubules and KHC. GFP-caytaxin expressed in hippocampal neurons is transported at a speed (∼1 μm/second) compatible with kinesin movement. Inhibition of kinesin-1 by dominant-negative KHC decreases the accumulation of caytaxin in the growth cone. Caytaxin puncta do not coincide with vesicles containing known kinesin cargos such as APP or JIP-1. A part of caytaxin, however, colocalizes with mitochondria and suppression of caytaxin expression by RNAi redistributes mitochondria away from the distal ends of neurites. These data indicate that caytaxin binds to kinesin-1 and functions as an adaptor that mediates intracellular transport of specific cargos, one of which is the mitochondrion.
Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis
Authors: Sigl Reinhard , Wandke Cornelia , Rauch Veronika , Kirk Jane , Hunt Tim , Geley Stephan
Published: October 2009

The anaphase-promoting complex/cyclosome (APC/C) is essential for progression through mitosis. At anaphase onset, the APC/C requires the activator protein CDC20 to target securin and cyclin B1 for proteasome-dependent degradation, but then depends on the CDC20-related protein FZR1 (also known as CDH1) to remain active until the onset of the next S phase. To investigate the role of FZR1 in mammalian cells, we used RNAi in human cell lines and conditional gene targeting in mouse embryonic fibroblasts. In neither case was FZR1 required for exit from mitosis, but in cells lacking FZR1, the G1 phase was shortened and the S phase was prolonged. In several normal and transformed human cell lines, loss of FZR1 function induced DNA-damage responses and impaired proliferation independently of the p53 status. Constitutive knockdown of p53 in U2OS cells with inducible FZR1 siRNA also failed to restore their proliferative capacity. Thus, the proliferation defects are a direct consequence of the genetic damage inflicted by loss of FZR1 function and are largely independent of p53. In summary, mammalian FZR1 is not required for the completion of mitosis, but is an important regulator of G1 phase and is required for efficient DNA replication in human and mouse somatic cells.
Frequenin/NCS-1 and the Ca2+-channel α1-subunit co-regulate synaptic transmission and nerve-terminal growth
Authors: Dason Jeffrey S. , Romero-Pozuelo Jesús , Marin Leo , Iyengar Balaji G. , Klose Markus K. , Ferrús Alberto , Atwood Harold L.
Published: October 2009

Drosophila Frequenin (Frq) and its mammalian and worm homologue, NCS-1, are Ca2+-binding proteins involved in neurotransmission. Using site-specific recombination in Drosophila, we created two deletions that removed the entire frq1 gene and part of the frq2 gene, resulting in no detectable Frq protein. Frq-null mutants were viable, but had defects in larval locomotion, deficient synaptic transmission, impaired Ca2+ entry and enhanced nerve-terminal growth. The impaired Ca2+ entry was sufficient to account for reduced neurotransmitter release. We hypothesized that Frq either modulates Ca2+ channels, or that it regulates the PI4Kβ pathway as described in other organisms. To determine whether Frq interacts with PI4Kβ with consequent effects on Ca2+ channels, we first characterized a PI4Kβ-null mutant and found that PI4Kβ was dispensable for synaptic transmission and nerve-terminal growth. Frq gain-of-function phenotypes remained present in a PI4Kβ-null background. We conclude that the effects of Frq are not due to an interaction with PI4Kβ. Using flies that were trans-heterozygous for a null frq allele and a null cacophony (encoding the α1-subunit of voltage-gated Ca2+ channels) allele, we show a synergistic effect between these proteins in neurotransmitter release. Gain-of-function Frq phenotypes were rescued by a hypomorphic cacophony mutation. Overall, Frq modulates Ca2+ entry through a functional interaction with the α1 voltage-gated Ca2+-channel subunit; this interaction regulates neurotransmission and nerve-terminal growth.
Modifying strain-hardening of carbon steels for improved finite element simulation of orthogonal machining
Authors: Childs T H C , Rahmad R
Published: October 2009

The results of finite element simulations of machining three carbon steels (BS970 070M20, 080M40, and 080M46), in the speed range 50–250 m/min and at an uncut chip thickness of 0.25 mm, are presented and compared with experimental results. It is shown that predictions of cutting forces and chip thickness ratios that are better than those obtained in many previous studies can be achieved by systematically changing the measured strain-hardening behaviour of the steels, to create materials with higher initial yield stress but unchanged flow stress at strains greater than 1.0. A justification for the change comes from earlier work that demonstrated an equivalence between that and including an upper yield point in the description of the initial yielding of the steel and which also shows that inclusion of an upper yield point is key to accurate predictions. The practical value of the paper is to show how improved simulations of machining may be obtained with commercial software packages without the need to create upper yield point material models.
Modelling and real-time compensation of cutting-force-induced error on a numerical control twin-spindle lathe
Authors: Wu H , Chen H J , Meng P , Yang J G
Published: October 2009

Cutting-force-induced errors are one of the major sources of error in numerical control (NC) machine tools. The error compensation technique is an effective way to improve the manufacturing accuracy of NC machine tools. Effective compensation relies on an accurate error model that can predict the errors exactly during the machining process. In the present paper a robust and accurate cutting-force-induced error model is built using a back-propagation (BP) neural network and a genetic algorithm (GA) for an NC twin-spindle lathe. The GA—BP neural network modelling technique not only enhances the prediction accuracy of the model but also reduces the training time of the BP neural network. A real-time compensation system of the cutting-force-induced error on the lathe is developed based on the cutting-force-induced error model. The errors were reduced by about 38 per cent after real-time compensation in a machining experiment.
Stability analysis in milling of thin-walled workpieces with emphasis on the structural effect
Authors: Zhang X-J , Xiong C-H , Ding Y , Zhang X-M
Published: October 2009

Regenerative chatter easily occurs in milling and has become the common limitation to achieve good surface quality and high productivity. For the purpose of chatter avoidance, the structural effect of the thin-walled part should be considered for the milling chatter stability analysis for the optimization of axial cutting depth and spindle speed pairs. The main objective of this paper is to examine the link between the structural modes (i.e. modal shapes) and the chatter stability limits in the case of finish milling thin-walled workpieces. In this paper, the dynamic stability of the milling process of thin-walled workpieces is investigated through a two-degree-of-freedom mechanical model. The mathematical relationship between the critical axial depth and the thin-walled part modal shapes is deduced and an optimal calculation process of milling stability lobes is presented. Peripheral milling of aluminium alloy (2A70 Al) plates is carried out on a computer numerically controlled (CNC) five-axis super high-speed machining centre to validate the method. The experimental results agree with the prediction by the presented method. Additionally, the experimental results show that the cutting stability is also influenced by the modal frequencies of the thin-walled part, which have a great influence on the milling stability analysis when the tool passing frequency (i.e. the inverse of the tooth passing period) harmonics are close to the modal frequencies of the part. The presented method is effective in the prediction of milling chatter limits in the thin-walled case for the optimization of machining parameters.
Hyperelastic materials modelling using a strain measure consistent with the strain energy postulates
Authors: Darijani H , Naghdabadi R , Kargarnovin M H
Published: October 2009

In this article, a strain energy density function of the Saint Venant—Kirchhoff type is expressed in terms of a Lagrangian deformation measure. Applying the governing postulates to the form of the strain energy density, the mathematical expression of this measure is determined. It is observed that this measure, which is consistent with the strain energy postulates, is a strain type with the characteristic function more rational than that of the Seth—Hill strain measures for hyperelastic materials modelling. In addition, the material parameters are calculated using a novel procedure that is based on the correlation between the values of the strain energy density (rather than the stresses) cast from the test data and the theory. In order to evaluate the performance of the proposed model of the strain energy density, some test data of pure homogeneous deformations are used. It is shown that there is a good agreement between the test data and predictions of the model for incompressible and compressible isotropic materials.
Performance analysis of an orthopaedic biomaterial 100-station wear test system
Authors: Saikko V
Published: October 2009

Until recently, wear studies of orthopaedic biomaterials have suffered from inadequate testing capacity and high standard deviation (SD) of results. In the present article, the previously validated 100-station hip wear simulator, the SuperCTPOD, is evaluated with regard to its capability of producing statistically significant differences in mean wear rates. SuperCTPOD wear tests were done for 38 different types of polyethylene pins against polished CoCr discs with diluted calf serum lubrication. A total of 200 pins were worn in two consecutive tests of 6 weeks, duration each. The sample size varied from four to six. The mean wear rates of the samples ranged from 0.52 to 77.1 mg per one million cycles. On the average, the SD of the wear rate was 4.2 per cent of the mean value (range 1–8.5 per cent). A difference in the mean wear rates below 5 per cent was large enough to be statistically significant ( p <0.05) in 21 comparisons between two samples, the lowest statistically significant mean difference being 3.2 per cent. In conclusion, the high capacity and the low SD of the wear rate make the SuperCTPOD wear test system unparalleled in efficiency. The observations regarding the effect of crosslinking and molecular weight on polyethylene wear resistance were in agreement with studies published earlier.
Dynamic analysis of multi-walled carbon nanotubes using the differential quadrature method
Authors: Hsu Ming-Hung
Published: October 2009

This work describes a novel modelling scheme to elucidate the frequencies of carbon nanotubes via continuum mechanics by considering the van der Waals force interaction based on differential quadrature simulations, in which nanobeam-bending paradigms are utilized. Exactly how the surrounding elastic medium, length-to-radius ratio, and van der Waals forces of the carbon nanotubes affect the frequencies is also investigated. The proposed modelling scheme is highly promising for advanced carbon nanotube applications. Further elucidation of the vibration mechanism of carbon nanotubes embedded in an elastic medium in this work significantly contributes to efforts to design nano oscillators.
A simplified method of calculating axial force for a permanent magnetic bearing
Authors: Jiang S , Liang Y , Wang H
Published: October 2009

Axial magnetic force is an important parameter for permanent magnetic bearing (PMB). Current mathematical models for modelling the magnetic force are too complicated on the basis of some assumptions. This article presents a simplified calculating model of the axial force for axially magnetized PMB using the typical method of magnetic conductance. In this method, the magnetic-reluctance coefficient needed is investigated with the parameter identification method. It shows that changing the structure parameters and magnet materials only affects the magnetic-reluctance coefficient in a comparatively small range. A test device for measuring the axial magnetic force of PMB is developed to verify the effectiveness of the simplified calculating method. The results show that the proposed method can clearly express the relation between the axial magnetic force and structure parameters of PMB and requires less computation cost when compared with previous conventional methods. In conclusion, the proposed method is simple and effective in computing the axial force for PMB.
The effect of micro-porous layers on the performance of proton exchange membrane fuel cells
Authors: Zhoufa H , Shenlong W , Mu P , Weng F-B , Hsu C-Y , Su A
Published: October 2009

Micro-porous layers (MPLs) of varying porosities were prepared on wet-proof carbon paper in order to investigate the effect of porosity on proton exchange membrane fuel cells. Pore size distribution in the gas diffusion electrode (GDE) layer was shown to have a bimodal distribution at approximately 0.01 and 0.08 μm. It appears that the smaller pores transfer gas and the larger pores remove water by capillary action. An appropriate amount of NH4Cl (50 wt%) in the MPL can therefore improve fuel cell performance because an optimum compromise can be found between water—gas transfer and internal resistance. Further increasing the NH4Cl content and porosity does not improve performance because internal resistance rises.
The influence of inlet swirling on the aeration performance of liquid jet gas pumps
Authors: El-Sallak M , Hefny M M
Published: October 2009

Several jet pumps with swirling components in the driving jet flow are investigated experimentally for using them in aeration systems. Experimental measurements were carried out for the mixing system model using atmospheric air to increase the dissolved oxygen in tap water under different operating conditions and with four different swirl components. The effects of water temperature, jet pump pressure ratio, and jet pump number are then investigated. The mixing performance is remarkably improved by using a swirling flow compared with the non-swirling cases. This improvement is noticed when the required saturation time is decreased and the gas transfer efficiency is increased. Moreover, the improvement is shown to increased in relation to the swirl intensity used.
Performance deterioration of the governing stage nozzle caused by solid particle erosion in the steam turbine
Authors: Wang S-S , Mao J-R , Liu G-W , Feng Z-P
Published: October 2009

In the steam turbine, solid particle erosion on a nozzle cascade is known to damage the profile and surface smoothness of the cascade, which increases the flow loss of steam. The present study aims to make clear the relations between nozzle loss and surface degradation, aerodynamic parameters, as well as the shape, location, and size of the erosion notch. A series of numerical simulations were conducted to model the aerodynamic performance of various existing eroded nozzles. The results indicate that the nozzle loss caused by the surface degradation shows an approximate linear decrease with an increase in notch depth. The nozzle loss caused by the erosion notch increases with either a decrease in the exit Mach number or an increase of the notch area. For the same erosion-induced weight loss of the nozzle, the asymmetric notch and local notch cause more nozzle loss than the symmetric notch and quasi-global notch. This means that the performance deterioration can be reduced to a minimum value if the erosion is uniform along the span-wise of the nozzle. In addition, a combined experimental and numerical investigation is conducted to explore the erosion damage process of the nozzle. The result suggests that the eroded nozzle should be replaced by a new nozzle before the notch begins to propagate.
The tedious task of finding homologous noncoding RNA genes
Authors: Menzel Peter , Gorodkin Jan , Stadler Peter F.
Published: October 2009

User-driven in silico RNA homology search is still a nontrivial task. In part, this is the consequence of a limited precision of the computational tools in spite of recent exciting progress in this area, and to a certain extent, computational costs are still problematic in practice. An important, and as we argue here, dominating issue is the dependence on good curated (secondary) structural alignments of the RNAs. These are often hard to obtain, not so much because of an inherent limitation in the available data, but because they require substantial manual curation, an effort that is rarely acknowledged. Here, we qualitatively describe a realistic scenario for what a “regular user” (i.e., a nonexpert in a particular RNA family) can do in practice, and what kind of results are likely to be achieved. Despite the indisputable advances in computational RNA biology, the conclusion is discouraging: BLAST still works better or equally good as other methods unless extensive expert knowledge on the RNA family is included. However, when good curated data are available the recent development yields further improvements in finding remote homologs. Homology search beyond the reach of BLAST hence is not at all a routine task.
Structural features of the tmRNA–ribosome interaction
Authors: Bugaeva Elizaveta Y. , Surkov Serhiy , Golovin Andrey V. , Öfverstedt Lars-Göran , Skoglund Ulf , Isaksson Leif A. , Bogdanov Alexey A. , Shpanchenko Olga V. , Dontsova Olga A.
Published: October 2009

Trans-translation is a process which switches the synthesis of a polypeptide chain encoded by a nonstop messenger RNA to the mRNA-like domain of a transfer-messenger RNA (tmRNA). It is used in bacterial cells for rescuing the ribosomes arrested during translation of damaged mRNA and directing this mRNA and the product polypeptide for degradation. The molecular basis of this process is not well understood. Earlier, we developed an approach that allowed isolation of tmRNA–ribosomal complexes arrested at a desired step of tmRNA passage through the ribosome. We have here exploited it to examine the tmRNA structure using chemical probing and cryo-electron microscopy tomography. Computer modeling has been used to develop a model for spatial organization of the tmRNA inside the ribosome at different stages of trans-translation.
The Arabidopsis thaliana double-stranded RNA binding protein DRB1 directs guide strand selection from microRNA duplexes
Authors: Eamens Andrew L. , Smith Neil A. , Curtin Shaun J. , Wang Ming-Bo , Waterhouse Peter M.
Published: October 2009

In Arabidopsis thaliana (Arabidopsis), DICER-LIKE1 (DCL1) functions together with the double-stranded RNA binding protein (dsRBP), DRB1, to process microRNAs (miRNAs) from their precursor transcripts prior to their transfer to the RNA-induced silencing complex (RISC). miRNA-loaded RISC directs RNA silencing of cognate mRNAs via ARGONAUTE1 (AGO1)-catalyzed cleavage. Short interefering RNAs (siRNAs) are processed from viral-derived or transgene-encoded molecules of double-stranded RNA (dsRNA) by the DCL/dsRBP partnership, DCL4/DRB4, and are also loaded to AGO1-catalyzed RISC for cleavage of complementary mRNAs. Here, we use an artificial miRNA (amiRNA) technology, transiently expressed in Nicotiana benthamiana, to produce a series of amiRNA duplexes with differing intermolecular thermostabilities at the 5′ end of duplex strands. Analyses of amiRNA duplex strand accumulation and target transcript expression revealed that strand selection (amiRNA and amiRNA*) is directed by asymmetric thermostability of the duplex termini. The duplex strand possessing a lower 5′ thermostability was preferentially retained by RISC to guide mRNA cleavage of the corresponding target transgene. In addition, analysis of endogenous miRNA duplex strand accumulation in Arabidopsisdrb1 and drb2345 mutant plants revealed that DRB1 dictates strand selection, presumably by directional loading of the miRNA duplex onto RISC for passenger strand degradation. Bioinformatic and Northern blot analyses of DCL4/DRB4-dependent small RNAs (miRNAs and siRNAs) revealed that small RNAs produced by this DCL/dsRBP combination do not conform to the same terminal thermostability rules as those governing DCL1/DRB1-processed miRNAs. This suggests that small RNA processing in the DCL1/DRB1-directed miRNA and DCL4/DRB4-directed sRNA biogenesis pathways operates via different mechanisms.
Transcription of the Dictyostelium discoideum mitochondrial genome occurs from a single initiation site
Authors: Le Phuong , Fisher Paul Robert , Barth Christian
Published: October 2009

Transcription of the mitochondrial genome in Dictyostelium discoideum gives rise to eight major polycistronic RNA species that can be detected by Northern hybridization. In order to determine whether these transcripts could possibly derive from processing of even larger transcripts, reverse transcriptase polymerase chain reactions (RT-PCRs) were performed in an attempt to amplify the intervening regions between the eight major transcripts. All but one intervening region were successfully reverse transcribed and amplified, indicating that even larger transcripts existed and that the eight major transcripts detected previously may be the products of transcript processing. Southern hybridization analyses of DNA fragments representing the sequences between the eight major transcripts with in vitro capped mitochondrial RNA identified the 5′ end of only one of the eight major transcripts as a genuine transcription start site. The ability to initiate transcription from DNA sequences upstream of the identified transcription initiation site was demonstrated in bacterial cells expressing the Dictyostelium mitochondrial RNA polymerase. We conclude that transcription of the Dictyostelium mitochondrial genome is initiated at a single site, generating a large polycistronic transcript that is very efficiently, probably cotranscriptionally processed into mature RNA species. This is the first report on a protist mitochondrial DNA that is, although much larger in size than its metazoan counterparts, transcribed from a single transcription initiation site.